PROPOLEOS Y CANCER
| Items 1 - 79 of 79 |
One page. |
| 1: Cancer Lett. 2006 Jan 10; [Epub ahead of print] |
Influence
of galangin on HL-60 cell proliferation and survival.
Bestwick
CS, Milne
L.
Molecular Nutrition Group, Gut Health Programme, Rowett Research Institute,
The effect of galangin, a flavonol component of
| 2: Life Sci. 2005 Dec 20; [Epub ahead of print] |
Therapeutic
effect of paclitaxel and propolis on lipid peroxidation and antioxidant system
in 7,12 dimethyl benz(a)anthracene-induced breast cancer in female Sprague
Dawley rats.
Padmavathi
R, Senthilnathan
P, Chodon
D, Sakthisekaran
D.
Department of Medical Biochemistry,
Breast cancer is one of the most common cancers in women of developed and
developing countries. The optimum management of which requires a multidisciplinary
approach including the use of certain biochemical and molecular markers. The
effect of propolis along with paclitaxel on 7,12 dimethyl benz(a)anthracene
(DMBA) induced experimental breast cancer was investigated in female Sprague
Dawley rats. Female Sprague Dawley rats were divided into five groups of six
animals each. Group I served as normal control animal. Group II animals received
DMBA (20 mg in 0.5 ml sunflower oil and 0.5 ml of saline) i.p. to develop
mammary tumor by the end of 90 days. Group III were breast cancer animals
treated with 33 mg paclitaxel/kg body weight (bw) weekly once for 4 weeks.
Group IV were breast cancer-bearing animals treated with 50 mg propolis/kg
bw for 30 days. Group V were breast cancer-bearing animals treated with both
paclitaxel and propolis as mentioned above. Administration of paclitaxel and
propolis effectively suppressed breast cancer, which is revealed by the decrease
in the extent of lipid peroxidation (LPO) with concomitant increase in the
activities of enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT)
and glutathione peroxidase (GPx)) and non-enzymic antioxidants (reduced glutathione
(GSH), Vitamin C and Vitamin E) levels when compared to breast cancer-bearing
animals treated with either paclitaxel or propolis alone. From our results,
we conclude that propolis is a potent antioxidant and, when given in combination
with paclitaxel, offers maximum protection against DMBA induced mammary carcinogenesis.
| 3: Am J Kidney Dis. 2005 Dec;46(6):e125-9. |
Acute renal
failure induced by a Brazilian variety of propolis.
Li YJ, Lin
JL, Yang
CW, Yu CC.
Department of Nephrology,
Propolis is a resinous substance collected by honeybees and used in hive construction
and maintenance. Cumulative evidence suggests that propolis may have anti-inflammatory,
antibiotic, antioxidant, antihepatotoxic, and antitumor properties. In addition
to topical applications, products containing propolis have been used increasingly
as dietary supplements. Although reports of allergic reactions are not uncommon,
propolis is reputed to be relatively nontoxic. Its systemic toxicity is rarely
reported and hence may be underestimated. This is the first report of propolis-induced
acute renal failure. A 59-year-old man required hemodialysis for acute renal
failure. The patient had cholangiocarcinoma and had ingested propolis for
2 weeks before presentation. Renal function improved after propolis withdrawal,
deteriorated again after reexposure, and then returned to a normal level after
the second propolis withdrawal. This case indicates that propolis can induce
acute renal failure and emphasizes the need for vigilance and care when propolis
is used as a medicine or dietary supplement.
PMID: 16310564 [PubMed - indexed for MEDLINE]
| 4: Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1252-61. |
Caffeic acid
phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to
ionizing radiation without affecting bone marrow radioresponse.
Chen
YJ, Liao
HF, Tsai
TH, Wang
SY, Shiao
MS.
Department of Radiation Oncology,
PURPOSE: Caffeic acid phenethyl ester (
| 5: Br J Pharmacol. 2005 Dec;146(8):1139-47. |
Caffeic acid
phenethyl ester modulates Helicobacter pylori-induced nuclear factor-kappa
B and activator protein-1 expression in gastric epithelial cells.
Abdel-Latif
MM, Windle
HJ, Homasany
BS, Sabra
K, Kelleher
D.
Department of Clinical Medicine, Dublin Molecular Medicine Centre and Trinity
Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland. abdellmm@tcd.ie
Caffeic acid phenethyl ester (CAPE), an active component of propolis from
honeybee hives (honeybee resin), has anti-inflammatory, anti-carcinogenic
and anti-bacterial properties. This study was designed to investigate the
anti-inflammatory effects of CAPE on Helicobacter pylori-induced NF-kappaB
and AP-
| 6: Cancer Lett. 2005 Oct 15; [Epub ahead of print] |
Dietary artepillin
C suppresses the formation of aberrant crypt foci induced by azoxymethane
in mouse colon.
Shimizu K, Das SK, Baba M, Matsuura Y, Kanazawa K.
Department of Life Science, Graduate
School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe
657-8501, Japan.
Artepillin C, a prenylated phenylpropanoid found specifically in Brazilian
propolis, has been shown to be a bioavailable antioxidant. In this study,
artepillin C was tested for colon cancer-preventing activity using azoxymethane-challenged
ddY mice. Oral doses of 80 and 160mg/kg body weight of propolis or 10mg/kg
of artepillin C (equi-amounts to 160mg propolis) reduced significantly the
frequency of colonic aberrant crypt foci (ACF) by 39.2, 43.7 and 43.4%, respectively.
In liver of the mice, glutathione S-transferase and NADPH:quinone reductase
activity increased with the doses of propolis or artepillin C, and an antioxidant-responsive
element (ARE) was found to be activated for binding DNA. Artepillin C is considered
to suppress the formation of colonic ACF through the activation of ARE and
induction of phase II enzymes in liver.
PMID: 16236434 [PubMed - as supplied by publisher]
| 7: Mol Carcinog. 2005 Dec;44(4):293-9. |
Artepillin
C in Brazilian propolis induces G(0)/G(1) arrest via stimulation of Cip1/p21
expression in human colon cancer cells.
Shimizu K, Das SK, Hashimoto T,
Sowa Y, Yoshida T, Sakai T, Matsuura Y, Kanazawa K.
Department of Life Science, Graduate
School of Science and Technology, Kobe University, Kobe, Japan.
Potential chemopreventive agents exist in foods. Artepillin C in Brazilian
propolis was investigated for its effects on colon carcinogenesis. We had
found that artepillin C was a bioavailable antioxidant, which could be incorporated
into intestinal Caco-2 and hepatic HepG2 cells without any conjugation and
inhibited the oxidation of intracellular DNA. Artepillin C was then added
to human colon cancer WiDr cells. It dose-dependently inhibited cell growth,
inducing G(0)/G(1) arrest. The events involved a decrease in the kinase activity
of a complex of cyclin D/cyclin-dependent kinase 4 and in the levels of retinoblastoma
protein phosphorylated at Ser 780 and 807/811. The inhibitors of the complex,
Cip1/p21 and Kip1/p27, increased at the protein level. On the other hand,
Northern blotting showed that artepillin C did not affect the expression of
Kip1/p27 mRNA. According to the experiments using isogenic human colorectal
carcinoma cell lines, artepillin C failed to induce G(0)/G(1) arrest in the
Cip1/p21-deleted HCT116 cells, but not in the wild-type HCT116 cells. Artepillin
C appears to prevent colon cancer through the induction of cell-cycle arrest
by stimulating the expression of Cip1/p21 and to be a useful chemopreventing
factor in colon carcinogenesis.
PMID: 16224795 [PubMed - indexed for MEDLINE]
| 8: J Nutr Biochem. 2005 Oct 5; [Epub ahead of print] |
Inhibitory
effects of caffeic acid phenethyl ester on cancer cell metastasis mediated
by the down-regulation of matrix metalloproteinase expression in human HT1080
fibrosarcoma cells.
Hwang
HJ, Park
HJ, Chung
HJ, Min
HY, Park
EJ, Hong
JY, Lee
SK.
Department of Pharmacy, College of Pharmacy, Ewha Woman's University, Seodaemun-Ku,
Seoul 120-750, South Korea.
Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been
used as a folk medicine. Recent study also revealed that CAPE has several
biological activities including antioxidation, anti-inflammation and inhibition
of tumor growth. The present study investigated the effect of CAPE on tumor
invasion and metastasis by determining the regulation of matrix metalloproteinases
(MMPs). Matrix metalloproteinases, which are zinc-dependent proteolytic enzymes,
play a pivotal role in tumor metastasis by cleavage of extracellular matrix
(ECM) as well as nonmatrix substrates. On this line, we examined the influence
of CAPE on the gene expression of MMPs (MMP-2, MMP-9, MT1-MMP), tissue inhibitor
of metalloproteinase-2 (TIMP-2) and in vitro invasiveness of human fibrosarcoma
cells. Dose-dependent decreases in MMP and TIMP-2 mRNA levels were observed
in CAPE-treated HT1080 human fibrosarcoma cells as detected by reverse transcriptase-polymerase
chain reaction (RT-PCR). Gelatin zymography analysis also exhibited a significant
down-regulation of MMP-2 and MMP-9 expression in HT1080 cells treated with
CAPE compared to controls. In addition, CAPE inhibited the activated MMP-2
activity as well as invasion, motility, cell migration and colony formation
of tumor cells. These data therefore provide direct evidence for the role
of CAPE as a potent antimetastatic agent, which can markedly inhibit the metastatic
and invasive capacity of malignant cells.
PMID: 16214327 [PubMed - as supplied by publisher]
| 9: Biol Pharm Bull. 2005 Oct;28(10):1928-33. |
Effects of
local administration of propolis and its polyphenolic compounds on tumor formation
and growth.
Orsolic
N, Terzic
S, Mihaljevic
Z, Sver
L, Basic
I.
Department of Animal Physiology, Faculty of Science, University of Zagreb;
10000 Zagreb, Rooseveltov trg 6, Croatia. norsolic@yahoo.com
Many dietary constituents are chemopreventive in animal models, and experiments
with cultured cells are revealing various potential mechanisms of action.
Compounds classified as blocking agents can prevent, or greatly reduce, initiation
of carcinogenesis, or suppressing agents can act on cell proliferation. Caffeic
acid (CA) and caffeic acid phenethyl ester (CAPE), members of the polyphenolic
compounds, are present in high concentrations in medicinal plants and propolis,
a natural beehive product. A water-soluble extract of propolis (WSDP) and
two components of propolis, CA and CAPE were investigated for direct antitumor
activity in vivo and in vitro. The local presence of CA and CAPE in the tissue
caused a significant delay in tumor formation and increased life span 29.30
to 51.73%, respectively. CA and CAPE, but not WSDP, significantly suppressed
human HeLa cervical carcinoma cell proliferation in vitro. Based on these
results, we postulate that the antitumor activity of polyphenolic compounds
includes direct cytotoxic effects on tumor cells.
PMID: 16204948 [PubMed - indexed for MEDLINE]
| 10: Biomed Pharmacother. 2005 Dec;59(10):561-70. Epub 2005 Aug 10. |
Antitumor,
hematostimulative and radioprotective action of water-soluble derivative of
propolis (WSDP).
Orsolic
N, Basic
I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, Croatia. norsolic@yahoo.com
Several studies suggest that dietary supplementation with antioxidant can
influence the response to chemotherapy as well as the development of adverse
side effects caused by treatment with chemotherapeutic agents. Using CBA mouse
model, we investigated a clinically potential use of a water-soluble derivative
of propolis (WSDP) in the treatment of various cytopenias induced by radiation
and/or chemotherapy. Also, the antimetastatic efficiency of WSDP given intraperitoneally
alone or in combination with chemotherapeutic agents and their effects on
the blood leukocytes count as well as on hematopoiesis were studied. Tumor
was a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the
lung were generated by injecting viable tumor cells intravenously (iv). WSDP
(50 or 150 mg/kg) exerted a significant antimetastatic effect (P < 0.001)
when given either before or after tumor cell inoculation. In combined treatment
WSDP and Epirubicin profoundly inhibited metastasis formation; this synergistic
effect is maximal when Epirubicin and WSDP were administrated after tumor
cell inoculation. Positive outcome of combined treatment with WSDP and Epirubicin
was also found regarding the number of red and white blood cells in peripheral
blood while in mice treated with Epirubicin alone the significant drop in
all hematological parameters was noticed on day 13 after tumor cell inoculation.
Furthermore, when WSDP (50 mg/kg) was given perorally (po) for 20 consecutive
days an increased number of exogenous CFUs was found in treated mice. WSDP
given either for 20 or 40 days increased cellularity of hematopoietic tissue
and the number of leucocytes in peripheral blood; prolonged treatment with
WSDP also elevated myeloid and megakaryocytic types of CFUs. To conclude,
these findings indicate that the combination of WSDP with chemotherapeutics
could increase the antimetastatic potential of chemotherapeutic agents; these
findings suggest the benefits of potential clinical trials using WSDP combined
with chemotherapeutic agents in order to maximize their antitumor activity
and minimize postchemotherapeutic or radiotherapeutic deteriorated reactions.
PMID: 16202559 [PubMed - indexed for MEDLINE]
| 11: Leuk Res. 2005 Nov;29(11):1343-6. |
Evaluation
of Manisa propolis effect on leukemia cell line by telomerase activity.
Gunduz C, Biray C, Kosova B, Yilmaz B, Eroglu Z, Sahin F, Omay SB, Cogulu O.
Ege University, Faculty of Medicine,
Department of Medical Biology, Izmir, Turkey.
Propolis is a resinous substance which is used by bees to repair and maintain
their hives. It has more than 180 compounds including flavonoids, phenolic
acids and its esters which have anti-inflammatory, antibacterial, antiviral,
immunomodulatory, antioxidant and antiproliferative effects. Propolis is shown
to inhibit cell division and protein synthesis. However the exact mechanism
underlying antitumor effect is not clearly described. On the other hand progressive
telomere shortening to a critical level results with senescence of normal
cells by inducing apoptosis and telomerase prevents erosion of telomeres.
In this study we aimed to evaluate hTERT ratios in propolis-treated T-cell
acute lymphoblastic leukemia (CCFR-CEM) cell line. Cell counts and cell viability
of propolis-treated and propolis-free T-cell acute lymphoblastic leukemia
(CCFR-CEM) cell line were assessed by trypan blue dye exclusion test and MTT
assay. The LightCycler instrument was used (online real-time PCR) for the
quantification of hTERT in CCFR-CEM cell line. The hTERT ratio significantly
decreased 60 and 93% after 24 and 72 h respectively compared to the initial
value of the cells incubated with propolis. It had almost no cytotoxic effect
and caused 30, 30, 22 and 12% decrease in cell counts after 24, 48, 72 and
96 h respectively which is statistically significant. In conclusion propolis
may show antitumor and apoptotic effect via inhibiting telomerase expression
besides the mechanisms which have been described previously.
PMID: 16055186 [PubMed - indexed for MEDLINE]
| 12: Int Immunopharmacol. 2005 Oct;5(11):1652-7. |
Effects of
Turkish pollen and propolis extracts on respiratory burst for K-562 cell lines.
Aliyazicioglu Y,
Deger O, Ovali E, Barlak Y, Hosver I, Tekelioglu Y,
Karahan SC.
Department of Biochemistry, Faculty
of Medicine, Ondokuz Mayis University, Samsun, 55139, Turkey.
Bee-collected pollen and propolis are apicultural products which are composed
of nutritionally valuable substances and contain considerable amounts of polyphenol
substances which may act as potent antioxidants. We wanted to show if respiratory
burst within a cancer cell lines could be influenced when incubated with pollen
and propolis extracts or not. Pollen and propolis extracts at concentrations
of 50, 25, 12.5 and 0 mg/ml were prepared by dimethyl sulfoxide (DMSO). K-562
cell cultures and mononuclear cell (MNC) cultures prepared from a peripheral
blood sample to serve as control cells were incubated with extracts for 24
h. Determination of respiratory burst was carried out by intracellular dichlorofluorescein
(DCFH) test by using flow-cytometric fluorescence analysis. While about 90%
and 66% fluorescence was detected at zero concentrations for both K-562 and
MNC cultures, fluorescence positivity decreased (between 3.8% and 11.8%) as
concentrations of both propolis and pollen extracts increased for K-562 cell
culture, but unchanged (between 20% and 83%) for MNC culture. It was concluded
that pollen and propolis extracts inhibit respiratory burst within cancer
cell lines probably by their antioxidant potentials.
PMID: 16039555 [PubMed - indexed for MEDLINE]
| 13: Clin Chim Acta. 2005 Dec;362(1-2):57-64. Epub 2005 Jul 6. |
Caffeic acid
phenyl ester in propolis is a strong inhibitor of matrix metalloproteinase-9
and invasion inhibitor: isolation and identification.
Jin UH, Chung TW, Kang SK, Suh SJ, Kim JK, Chung KH, Gu YH, Suzuki I, Kim CH.
Department of Biochemistry and
Molecular Biology, Dongguk University College of Oriental Medicine and National
Research Laboratory for Glycobiology, Kyungbuk, Korea.
BACKGROUND: Propolis has been used as a folk medicine and has several proven
biological activities. Herbal remedies recommended for cancer therapies in
Korea. METHODS: Matrix metalloproteinase (MMP)-9-inhibitory activity of propolis
has been assessed. CAPE as an acting compound was isolated and molecular structure
was determined. Anti-invasion activity of CAPE was assayed using hepatocarcinoma
cells. RESULTS: Propolis ethanol extracts showed a strong inhibitory effect
of MMP-9 activity, which is known to be involved in tumor cell invasion and
metastasis in a concentration-dependent manner on zymography. Assay guided
fractionation led to the isolation of a caffeic acid phenyl ester (CAPE) as
the compound responsible for the anti-MMP-9 activity. CAPE was obtained by
reversed-phase HPLC, and its structure was elucidated by fast atom bombardment
mass spectrometry and tandem mass spectrometry. The purified CAPE inhibited
MMP-9 activity with the IC(50) of 1.0-2.0 nmol/l. CONCLUSIONS: CAPE possesses
selective antiproliferative activity toward hepatocaricoma cell line Hep3B,
but not primary cultured mouse hepatocytes.
PMID: 16004979 [PubMed - indexed for MEDLINE]
| 14: Biol Pharm Bull. 2005 Jun;28(6):1025-30. |
Two related
cinnamic Acid derivatives from Brazilian honey bee propolis, baccharin and
drupanin, induce growth inhibition in allografted sarcoma s-
Mishima S, Ono Y, Araki Y, Akao Y, Nozawa Y.
API Co. Ltd., R&D, Gifu,
Japan.
Honey bee propolis is rich in cinnamic acid derivatives. Baccharin and drupanin
from Brazilian honey bee propolis are cinnamic acid derivatives that contain
prenyl moieties. We previously isolated these two compounds and demonstrated
that they induce an apoptotic event in several tumor cell lines. In this study,
we examined the tumoricidal activity of baccharin and drupanin in mice allografted
with sarcoma S-180 and also studied the genotoxic effects on normal splenocytes
using the alkaline single cell gel (comet) assay. We found that both baccharin
and drupanin effectively suppressed growth of the tumor. Furthermore, these
compounds induced a significant genotoxic effect on the tumor cells in comparison
with normal splenocytes. Thus, baccharin and drupanin are potent tumor suppressive
components of honeybee propolis.
PMID: 15930739 [PubMed - indexed for MEDLINE]
| 15: Biochem Pharmacol. 2005 Jun 15;69(12):1815-27. |
Chrysin induces
G1 phase cell cycle arrest in C6 glioma cells through inducing p21Waf1/Cip1
expression: involvement of p38 mitogen-activated protein kinase.
Weng
MS, Ho YS, Lin
JK.
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine,
National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 10018, Taiwan.
Flavonoids are a broadly distributed class of plant pigments, universally
present in plants. They are strong anti-oxidants that can inhibit carcinogenesis
in rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active
compound extracted from many plants, honey, and propolis. It possesses potent
anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing
cell cycle progression. However, the mechanism by which chrysin inhibits cancer
cell growth remains poorly understood. Therefore, we developed an interest
in the relationship between MAPK signaling pathways and cell growth inhibition
after chrysin treatment in rat C6 glioma cells. Cell viability assay and flow
cytometric analysis suggested that chrysin exhibited a dose-dependent and
time-dependent ability to block rat C6 glioma cell line cell cycle progression
at the G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation
in C6 glioma cells exposed to 30 microM chrysin for 24h decreased significantly.
We demonstrated the expression of cyclin-dependent kinase inhibitor, p21(Waf1/Cip1),
to be significantly increased, but the p53 protein level did not change in
chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4 (CDK4)
kinase activities were reduced by chrysin in a dose-dependent manner. Furthermore,
chrysin also inhibited proteasome activity. We further showed that chrysin
induced p38-MAPK activation, and using a specific p38-MAPK inhibitor, SB203580,
attenuated chrysin-induced p21(Waf1/Cip1) expression. These results suggest
that chrysin exerts its growth-inhibitory effects either through activating
p38-MAPK leading to the accumulation of p21(Waf1/Cip1) protein or mediating
the inhibition of proteasome activity.
PMID: 15869744 [PubMed - indexed for MEDLINE]
| 16: J Dent Res. 2005 May;84(5):468-73. |
Properties
of BK(Ca) channels in oral keratinocytes.
Shieh DB, Yang SR, Shi XY, Wu YN, Wu SN.
Institute of Oral Medicine, National
Cheng Kung University Medical College, No. 1, University Road, Tainan 701,
Taiwan.
Keratinocytes are important for epithelial antimicrobial barrier function.
The activity of ion channels can affect the proliferation of keratinocytes.
Little is known about Ca2+-activated K+ currents in these cells. Ion currents
in normal human oral keratinocytes were characterized with a patch-clamp technique.
In whole-cell configuration, depolarizing pulses evoked K+ outward currents
(I(K)) in oral keratinocytes. Iberiotoxin (200 nM) and paxilline (1 microM)
suppressed I(K); however, neither apamin (200 nM) nor 5-hydroxydecanoate (30
microM) had any effects on it. Caffeic acid phenethyl ester, a compound of
honeybee propolis, increased I(K) with an EC50 value of 12.8 +/- 1.2 microM.
In inside-out patches, a BK(Ca) channel was observed in keratinocytes, but
not in oral squamous carcinoma (OCE-M1) cells. Caffeic acid phenethyl ester
or cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate applied to the intracellular
surface of a detached patch increased BK(Ca)-channel activity. The results
demonstrate that the properties of BK(Ca) channels in normal human oral keratinocytes
are similar to those described in other types of cells. Caffeic acid derivatives
can also stimulate BK(Ca)-channel activity directly.
PMID: 15840785 [PubMed - indexed for MEDLINE]
| 17: Biol Pharm Bull. 2005 Apr;28(4):694-700. |
Synergistic
antitumor effect of polyphenolic components of water soluble derivative of
propolis against Ehrlich ascites tumour.
Orsolic
N, Kosalec
I, Basic
I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Croatia.
Effect of two preparation (Croatian and Brazilian) of water-soluble derivative
of propolis (WSDP), caffeic acid, quercetin, chrysin, naringenin (components
present in WSDP) on the development of Ehrlich ascites tumour (EAT) was evaluated.
Test components (50 mg/kg) were given perorally or intraperitoneally 2 h prior
the intraperitonel injection of EAT (2 x 10(6)) cells. It was observed that
all test compounds effectively inhibited tumour growth and the proliferation
of EAT. The volume of ascitic fluid induced by EAT cells and total number
of cells present in the peritoneal cavity was markedly reduced in EAT-bearing
mice treated with test components. In treated mice the number of polymorphonuclear
(PMN) cells in the peritoneal cavity was increased while the number of macrophages
was decreased. The macrophage spreading activity revealed that WSDP and all
test compounds affected the functional state of macrophages increasing their
tumorcidal activity; the effect of WSDP was most pronounced indicating synergistic
effect of components present in WSDP. Antitumor activity of WSDP may be the
result of different specific mechanism(s) of flavonoids present as compared
to individual flavonoid given alone. It is likely that the part of antitumor
efficacy of test components against EAT cells was the results of increased
activity of macrophages.
PMID: 15802812 [PubMed - indexed for MEDLINE]
| 18: Nat Prod Res. 2005 Feb;19(2):183-8. |
Natural product
propolis: chemical composition.
Sahinler
N, Kaftanoglu
O.
Mustafa Kemal University, Faculty of Agriculture, Department of Animal Science,
Hatay, Turkey. nsahinler@mku.edu.tr
The chemical composition of propolis from East Mediterranean (Hatay, Adana
and Mersin) was studied in order to determine the major compounds by using
GC-MS. In this study, the ethanolic extract of propolis prepared by mixing
1900mL 70% ethanol and 100g propolis was used. Chemical analysis of propolis
extracts indicated that the propolis samples had high concentrations of the
aromatic acids, esters and other derivatives which are responsible for the
anti-bacterial, anti-fungal, anti-viral, anti-inflammatory and anti-cancer
properties of propolis such as benzyl cinnamate, methyl cinnamate, caffeic
acid, cinnamyl cinnamate and cinnamoylglcine besides the most common compounds
as fatty acid, terpenoids, esters, alcohols hydrocarbons and aromatic acids.
PMID: 15715264 [PubMed - indexed for MEDLINE]
| 19: FEBS Lett. 2005 Jan 31;579(3):705-11. |
Chrysin suppresses
lipopolysaccharide-induced cyclooxygenase-2 expression through the inhibition
of nuclear factor for IL-6 (NF-IL6) DNA-binding activity.
Woo KJ, Jeong YJ, Inoue H, Park JW, Kwon TK.
Department of Immunology, School
of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712,
South Korea.
Chrysin is a natural, biologically active compound extracted from many plants,
honey and propolis. It possesses potent anti-inflammation, anti-cancer and
anti-oxidation properties. The mechanism by which chrysin suppresses COX-2
expression remains poorly understood. In the present report, we investigated
the effect of chrysin on the expression of COX-
| 20: Ann N Y Acad Sci. 2004 Dec;1030:501-7. |
Inhibition
of cyclooxygenase-2 expression and restoration of gap junction intercellular
communication in H-ras-transformed rat liver epithelial cells by caffeic acid
phenethyl ester.
Lee KW, Chun KS, Lee JS, Kang KS, Surh YJ, Lee HJ.
Department of Food Science and
Technology, School of Agricultural Biotechnology, Seoul National University,
Seoul 151-742, South Korea.
One of the most frequent defects in human cancers is the uncontrolled activation
of the ras signaling pathways. Increased expression of cyclooxygenase-2 (COX-2)
and inhibition of gap junction intercellular communication (GJIC) have been
frequently observed in several forms of human malignancies. The present study
investigated the effects of caffeic acid phenethyl ester (CAPE), a chemopreventive
phytochemical derived from honey propolis, on COX-2 expression and GJIC in
Harvey-ras-transformed WB-F344 rat liver epithelial cells (H-ras WB cells).
H-ras induced COX-2 expression in WB-F344 rat liver epithelial cells (WB cells).
H-ras WB cells also exhibited complete inhibition of GJIC and predominant
unphosphorylation of connexin 43 (Cx43), a major protein modulating GJIC.
CAPE significantly inhibited the constitutive expression of COX-2 and restored
the disrupted GJIC through the phosphorylation of Cx43 at a concentration
of 12.5 microM in H-ras WB cells. Although the molecular basis for the cancer
chemopreventive activity of CAPE is not completely understood, several studies
suggest that CAPE is a potent and specific inhibitor of the transcription
factor nuclear factor kappaB (NF-kappaB) activation. We also found that CAPE
significantly inhibited H-ras-induced NF-kappaB DNA-binding activity without
affecting the activation of extracellular signal-regulated kinase and p38
mitogen-activated protein kinase, which are major intracellular molecules
involved in the Ras signaling pathways. In conclusion, CAPE may exert cancer
chemopreventive effects through the inhibition of COX-2 expression and the
restoration of disrupted GJIC induced by H-ras, possibly by targeting NF-kappaB.
PMID: 15659835 [PubMed - indexed for MEDLINE]
| 21: Environ Mol Mutagen. 2005;45(1):8-16. |
Modifying
effect of propolis on dimethylhydrazine-induced DNA damage but not colonic
aberrant crypt foci in rats.
de Lima RO, Bazo AP, Said RA, Sforcin JM, Bankova V, Darros BR, Salvadori DM.
Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista,
Botucatu, Sao Paulo, Brazil.
Propolis is a honeybee product
with several biological and therapeutic properties, including antimutagenic
and anticarcinogenic activities. The effects of an aqueous extract of propolis
(AEP) were evaluated on the formation of 1,2-dimethylhydrazine (DMH)-induced
aberrant crypt foci (ACF) and DNA damage in the colon of male Wistar rats
by the ACF and Comet assays, respectively. AEP was administered orally at
0.01%, 0.03%, 0.1%, and 0.3% in the drinking water, which resulted in doses
of approximately 12, 34, 108, and 336 mg/kg body weight/day. Animals were
also given a single subcutaneous injection of 40 mg/kg DMH and sacrificed
4 hr later for evaluating DNA damage, or 4 doses of 40 mg/kg DMH, administered
2 doses/week for 2 weeks, and sacrificed 12 weeks after the last injection
for evaluating ACF development in the distal colon. Administration of AEP
either simultaneously with or after the DMH treatment resulted in no statistically
significant reduction of ACF. In contrast, 0.01%, 0.03%, and 0.3% AEP, given
simultaneously with DMH, reduced DNA damage induction in the mid and distal
colon. However, 0.3% AEP alone increased DNA damage in the colon. In conclusion,
AEP had no effect on the formation of DMH-induced ACF in rat colon, but it
modulated DMH-induced DNA damage in colon cells. Further investigations are
recommended in order to establish the conditions under which propolis produces
either protective or deleterious effects. 2004
Wiley-Liss, Inc.
PMID: 15605358 [PubMed - indexed for MEDLINE]
| 22: Life Sci. 2004 Dec 17;76(5):545-58. |
Chilean propolis:
antioxidant activity and antiproliferative action in human tumor cell lines.
Russo A, Cardile V, Sanchez F, Troncoso N, Vanella A, Garbarino JA.
Department of Biological Chemistry,
Medical Chemistry and Molecular Biology, University of Catania, v.le A. Doria
6, 95125 Catania-Italy. alrusso@unict.it
Propolis, a natural product derived from plant resins collected by honeybees,
has been used for thousands of years in traditional medicine all over the
world. The composition of the propolis depends upon the vegetation of the
area from where it was collected and on the bee species. In this study, we
investigated the antioxidant activity of a propolis sample, provided by NATURANDES-CHILE,
collected in a temperate region of central Chile. In addition, this natural
compound was tested for its antiproliferative capacity on KB (human mouth
epidermoid carcinoma cells), Caco-2 (colon adenocarcinoma cells) and DU-145
(androgen-insensitive prostate cancer cells) human tumor cell lines. Results
showed that this Chilean propolis sample exhibits interesting biological properties,
correlated with its chemical composition and expressed by its capacity to
scavenge free radicals and to inhibit tumor cell growth.
PMID: 15556167 [PubMed - indexed for MEDLINE]
| 23: Biochem Biophys Res Commun. 2004 Dec 24;325(4):1215-22. |
Chrysin-induced
apoptosis is mediated through caspase activation and Akt inactivation in U937
leukemia cells.
Woo
KJ, Jeong
YJ, Park
JW, Kwon
TK.
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong
Jung-Gu, Taegu 700-712, Republic of Korea. kwontk@dsmc.or.kr
Chrysin is a natural, biologically active compound extracted from many plants,
honey, and propolis. It possesses potent anti-inflammation, anti-cancer, and
anti-oxidation properties. The mechanism by which chrysin initiates apoptosis
remains poorly understood. In the present report, we investigated the effect
of chrysin on the apoptotic pathway in U937 human promonocytic cells. We show
that chrysin induces apoptosis in association with the activation of caspase
3 and that Akt signal pathway plays a crucial role in chrysin-induced apoptosis
in U937 cells. Furthermore, we have shown that inhibition of Akt phosphorylation
in U937 cells by the specific PI3K inhibitor, LY294002 significantly, enhanced
apoptosis. Overexpression of a constitutively active Akt (myr-Akt) in U937
cells inhibited the induction of apoptosis, activation of caspase 3, and PLC-gamma1
cleavage by chrysin. Together, these findings suggest that the Akt pathway
plays a major role in regulating the apoptotic response of human leukemia
cells to chrysin and raise the possibility that combined interruption of chrysin
and PI3K/Akt-related pathways may represent a novel therapeutic strategy in
hematological malignancies.
PMID: 15555556 [PubMed - indexed for MEDLINE]
| 24: Oncol Res. 2004;14(9):415-26. |
Resveratrol and
propolis as necrosis or apoptosis inducers in human prostate carcinoma cells.
Scifo
C, Cardile
V, Russo
A, Consoli
R, Vancheri
C, Capasso
F, Vanella
A, Renis
M.
Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology,
University of Catania, Viale Andrea Doria, 6, 95125 Catania, Italy.
Vegetables and fruit help the prevention and the therapy of several kinds
of cancer because they contain micronutrients, a class of substances that
have been shown to exhibit chemopreventive and chemotherapeutic activities.
In the present study the effects of resveratrol (100 and 200 microM), a phytoalexin
found in grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml),
a natural honeybee hive product, were tested in androgen-resistant prostate
cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma.
A comparison between the activity of these micronutrients and vinorelbine
bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy
of prostate cancer, was conducted. Several biochemical parameters were tested,
such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase
release), cell redox status (nitric oxide formation, reactive oxygen species
production, reduced glutathione levels), genomic DNA fragmentation (COMET
assay) with special attention on the presence of apoptotic DNA damage (TUNEL
test), and possible mitochondrial transmembrane potential alteration (deltapsi).
Our results point out the anticancer activity of resveratrol and propolis
extract in human prostate cancer, exerting their cytotoxicity through two
different types of cell death: necrosis and apoptosis, respectively. The data
obtained suggest the possible use of these micronutrients both in alternative
to classic chemotherapy, and in combination with very low dosage of vinorelbine
(5 microM).
PMID: 15490973 [PubMed - indexed for MEDLINE]
| 25: J Agric Food Chem. 2004 May 19;52(10):3083-8. |
Identification
of metabolites in plasma and urine of Uruguayan propolis-treated rats.
Kumazawa S, Shimoi K, Hayashi K, Ishii T, Hamasaka T, Nakayama T.
Laboratory of Functional Food
Science and COE Program in the 21st Century, School of Food and Nutritional
Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. kumazawa@smail.u-shizuoka-ken.ac.jp
Propolis is a resinous substance collected by honeybees from various plant
sources. It is extensively used in food and beverages to improve health and
prevent diseases such as heart disease, diabetes, and cancer. To investigate
the absorption and metabolism of the components in propolis, in the present
study, we administered ethanol extracts of Uruguayan propolis (poplar type
propolis) orally to rats and analyzed their plasma and urine by high-performance
liquid chromatography with photodiode array and mass spectrometric detection.
After deconjugation of the components by beta-glucuronidase/sulfatase treatment
of the specimen, pinobanksin 5-methyl ether, pinobanksin, kaempferol, chrysin,
pinocembrin, and galangin were detected in plasma of rats orally administered
propolis. These compounds were detected also in urine after beta-glucuronidase/sulfatase
treatment. Furthermore, pinobanksin 5-methyl ether, pinobanksin, chrysin,
pinocembrin, and galangin were present in the urine also in free form. These
results suggest that flavonoids in propolis are metabolized and circulate
in the body after oral administration of propolis.
PMID: 15137857 [PubMed - indexed for MEDLINE]
| 26: Biol Pharm Bull. 2004 May;27(5):727-30. |
Inhibitory
effect of propolis on the growth of human leukemia U937.
Aso
K, Kanno
S, Tadano
T, Satoh
S, Ishikawa
M.
Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku
Pharmaceutical University, Sendai, Japan.
We have investigated the effect of propolis (CB Propolis) on the growth of
human histiocytic lymphoma U937 cells. We found that propolis strongly inhibited
the growth of the cells and macromolecular synthesis in a dose- and time-dependent
manner by apoptosis. Propolis at 0.015-0.5 microl/ml showed antitumor activity
with an IC(50) of 0.18 microl/ml for 3 d. It also inhibits DNA, RNA and protein
synthesis with an IC(50) of 0.08, 0.17 and 4.3 microl/ml, respectively. The
inhibitory effect on DNA synthesis was partially irreversible. Moreover, an
apoptotic DNA ladder and chromatin condensation were observed in the same
concentration range in which cell growth was inhibited. The caspase inhibitor,
Z-Asp-CH(2)-DCB, prevented DNA fragmentation. These results suggest that the
antitumor activity of propolis occurs through the induction of apoptosis.
Propolis may be useful as a cancer chemopreventive and chemotherapeutic agent.
PMID: 15133255 [PubMed - indexed for MEDLINE]
| 27: J Exp Zoolog A Comp Exp Biol. 2004 May 1;301(5):389-400. |
Stage-dependent
modulation of limb regeneration by caffeic acid phenethyl ester (CAPE)--immunocytochemical
evidence of a CAPE-evoked delay in mesenchyme formation and limb regeneration.
Brudzynski
K, Carlone
R.
Bee-Biomedicals Inc. St. Catharines, Ontario, Canada L2T 3T4.
Caffeic acid phenethyl ester (CAPE), a natural compound of bee propolis, selectively
inhibits proliferation of transformed cells in several cancer models in vitro.
To examine in vivo CAPE function, we used the newt regeneration blastema as
a model system wherein the processes of de-differentiation and subsequent
proliferation of undifferentiated cells mimic changes associated with oncogenic
transformation and tumorigenesis. We have shown that a single dose of CAPE
significantly increased cell proliferation at the stages of blastema growth
and re-differentiation. At the de-differentiation stage, CAPE significantly
stimulated proliferation of wound epidermis keratinocytes, but decreased proliferation
in the blastema mesenchyme. Immunohistochemistry with a mesenchymal cell marker,
vimentin, revealed a highly significant reduction of vimentin staining in
the mesenchyme of CAPE-treated regenerates (p<0.001). These results, together
with morphological observations indicate that, at the de-differentiation stage,
CAPE stimulated wound re-epithelization, increased keratinocyte proliferation
and increased thickness of the wound epidermis. However, CAPE inhibited mesenchyme
formation and proliferation. The functional consequence of the CAPE inhibitory
action was a delay in limb regeneration. Copyright
2004 Wiley-Liss, Inc.
PMID: 15114646 [PubMed - indexed for MEDLINE]
| 28: Nutr Cancer. 2003;47(2):156-63. |
Inhibitory effect
of water-soluble derivative of propolis and its polyphenolic compounds on
tumor growth and metastasizing ability: a possible mode of antitumor action.
Orsolic
N, Sver
L, Terzic
S, Tadic
Z, Basic
I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Zagreb, Croatia. norsolic@yahoo.com
Polyphenolic compounds are widely distributed in the plant kingdom and display
a variety of biological activities, including chemoprevention and tumor growth
inhibition. Propolis is made up of a variety of polyphenolic compounds. We
compared how the routes of administration of polyphenolic compounds deriving
from propolis and of propolis itself affect the growth and metastatic potential
of a transplantable mammary carcinoma (MCa) of the CBA mouse. The influence
of tested compounds on local tumor growth was also studied. Metastases in
the lung were generated by 2 x 10(5) tumor cells injected intravenously (IV).
A water-soluble derivative of propolis (WSDP) and polyphenolic compounds (caffeic
acid, CA, and CA phenethyl ester, CAPE) were given to mice per os (PO) or
intraperitoneally (IP) before or after tumor cell inoculation. Tested compounds
significantly decreased the number of lung colonies. When mice were inoculated
with 10(5) MCa cells in the exact site of subcutaneous injection of different
doses of WSDP, CA, or CAPE, tumor growth was inhibited, and survival of treated
mice was prolonged. Antitumor activity, according to the results obtained,
is mostly related to the immunomodulatory properties of the compounds and
their capacity to induce apoptosis and necrosis. In conclusion, results presented
here indicate that WSDP, CA, and CAPE could be potential useful tools in the
control of tumor growth in experimental tumor models when administrated PO;
because PO administration is the easiest way of introducing a compound used
for prevention and/or cure of any disease, it is likely that this article
has reached the goal of the investigation.
PMID: 15087268 [PubMed - indexed for MEDLINE]
| 29: Arch Biochem Biophys. 2004 Apr 15;424(2):181-8. |
Antioxidative
bioavailability of artepillin C in Brazilian propolis.
Shimizu
K, Ashida
H, Matsuura
Y, Kanazawa
K.
Department of Life Science, Graduate School of Science and Technology, Kobe
University, Rokkodai, Nada-ku, Kobe 657-8501, Japan.
Propolis has strong antioxidative activity. We investigated here whether this
activity was available in intestinal Caco-2 and hepatic HepG2 cells. Phenolics
in Brazilian propolis, extracted with ethyl acetate after the removal of resin
and wax with 90% methanol, included artepillin C at 21 mmol/100 g, p-coumaric
acid and cinnamic acid relatives 24mmol, kaempferol and its derivatives 9.4
mmol, naringenin 2.8 mmol, isosakuranetin 0.9 mmol, chrysin at 0.8 mmol/100
g, and several minor components. When the extract was added to the apical
side of Caco-2 monolayers, artepillin C was specifically incorporated into
the cells and released to the basolateral side mostly without conjugation.
Then, artepillin C was added to HepG2 cells and exposed to reactive oxygens.
Artepillin C prevented oxidative damage dose-dependently, and suppressed lipid
peroxidation evaluated with thiobarbituric acid reactive substances by 16%
and the formation of 8-hydroxy-2'-deoxyguanosine in DNA by 36% at a concentration
of 20microM. Artepillin C is a bioavailable antioxidant.
PMID: 15047190 [PubMed - indexed for MEDLINE]
| 30: J Med Food. 2003 Winter;6(4):387-90. |
Effects of
chrysin on urinary testosterone levels in human males.
Gambelunghe
C, Rossi
R, Sommavilla
M, Ferranti
C, Rossi
R, Ciculi
C, Gizzi
S, Micheletti
A, Rufini
S.
Department of Clinical and Experimental Medicine, Division of Sports Medicine-Laboratorio
delle Attivita Motorie e Sportive, University of Perugia, Perugia, Italy.
labsport@unipg.it
The equilibrium of sexual hormones in both sexes is controlled in vertebrates
by the enzyme aromatase, a member of the cytochrome P450 superfamily, which
catalyzes the conversion of androstenedione and testosterone into estrone
and estradiol, respectively. Flavonoids are diphenolic compounds present in
whole grains, legumes, fruits, and vegetables that are strongly implicated
as protective in coronary heart disease, stroke, and cancer. One flavonoid,
chrysin, found in high concentrations in honey and propolis, has been shown
to be an inhibitor of aromatase enzyme activity. These foods are often used
as supplements, particulary by sportsmen for their energetic and antioxidant
properties. The aim of this study was to verify if daily treatment for 21
days with propolis and honey, containing chrysin, would modify urinary concentrations
of testosterone in volunteer male subjects. In fact, aromatase inhibition
by chrysin could block the conversion of androgens into estrogens with a consequent
increase of testosterone, eventually measurable in urine samples. The obtained
data did not show alterations of the levels of testosterone in the volunteers
after 7, 14, and 21 days of treatment in comparison with baseline values and
compared with measurements on the control subjects at the same time. In conclusion,
the use of these foods for 21 days at the doses usually taken as oral supplementation
does not have effects on the equilibrium of testosterone in human males.
PMID: 14977449 [PubMed - indexed for MEDLINE]
| 31: J Agric Food Chem. 2003 Dec 31;51(27):7907-12. |
Inhibitory
effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and
metastasis.
Liao HF, Chen YY, Liu JJ, Hsu ML, Shieh HJ, Liao HJ, Shieh CJ, Shiao MS, Chen YJ.
Department of Medical Research
and Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan.
Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been
used as a folk medicine and has several proven biological activities. The
present study investigated the effect of CAPE on angiogenesis, tumor invasion,
and metastasis. A cytotoxicity assay of CAPE in CT26 colon adenocarcinoma
cells showed a dose-dependent decrease in cell viability but no significant
influence on the growth of human umbilical vein epithelial cells (HUVEC).
A low concentration of CAPE (1.5 microg/mL) inhibited 52.7% of capillary-like
tube formation in HUVEC culture on Matrigel. CAPE (6 microg/mL)-treated CT26
cells showed not only inhibited cell invasion by 47.8% but also decreased
expression of matrix metalloproteinase (MMP)-2 and -9. Vascular endothelial
growth factor (VEGF) production from CT26 cells was also inhibited by treatment
with CAPE (6 microg/mL). Intraperitoneal injection of CAPE (10 mg/kg/day)
in BALB/c mice reduced the pulmonary metastatic capacity of CT26 cells accompanied
with a decreased plasma VEGF level. CAPE treatment also prolonged the survival
of mice implanted with CT26 cells. These results indicate that CAPE has potential
as an antimetastatic agent.
PMID: 14690372 [PubMed - indexed for MEDLINE]
| 32: Biochem Pharmacol. 2004 Jan 1;67(1):53-66. |
Propolin
C from propolis induces apoptosis through activating caspases, Bid and cytochrome
c release in human melanoma cells.
Chen
CN, Wu CL, Lin
JK.
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine,
National Taiwan University, Section 1, Jen-Ai Road, 100, ROC, Taipei, Taiwan.
We had demonstrated that two prenylflavanones, propolin A and propolin B,
isolated and characterized from Taiwanese propolis, induced apoptosis in human
melanoma cells and significantly inhibited xanthine oxidase activity. Here,
we have isolated a third compound called propolin C. The chemical structure
of propolin C has been characterized by NMR and HRMS spectra, and was identical
to nymphaeol-A. However, no biological activities of this compound have ever
been reported. In the present study, propolin C effectively induced a cytotoxic
effect on human melanoma cells, with an IC(50) of about 8.5 microM. DNA flow
cytometric analysis indicated that propolin C actively induced apoptosis in
human melanoma cells and there is a marked loss of cells from the G2/M phase
of the cell cycle. To address the mechanism of the apoptosis effect of propolin
C, we evaluated the effect of propolin C on induction of apoptosis-related
proteins in human melanoma cells. The levels of procaspase-8, Bid, procaspase-3,
and poly(ADP-ribose) polymerase were decreased in dose- or time course-dependent
manners. Moreover, propolin C was capable of releasing cytochrome c from mitochondria
to cytosol. The findings suggest that propolin C may activate a mitochondria-mediated
apoptosis pathway. On other hand, propolin C is a potential antioxidant agent
and shows a strong capability to scavenge free radicals and inhibit on xanthine
oxidase activity with IC(50) of about 17.0microM. In conclusion, the isolation
and characterization of propolin C from bee propolis are described for the
first time, and this compound is a powerful inducer of apoptosis in human
melanoma cells.
PMID: 14667928 [PubMed - indexed for MEDLINE]
| 33: Mutat Res. 2003 Nov;544(2-3):195-201. |
Dietary components
may prevent mutation-related diseases in humans.
Ribeiro LR, Salvadori DM.
Programa de Pos-Graduacao
Publication Types:
· Review
PMID: 14644321 [PubMed - indexed for MEDLINE]
| 34: Clin Chim Acta. 2003 Dec;338(1-2):11-6. |
Protective role of Egyptian
propolis against tumor in mice.
El-khawaga OA,
Salem TA, Elshal MF.
Chemistry Department, Faculty of Science, Mansoura University, Mansoura City,
Egypt. elkhawaga70s@mans.edu.eg
BACKGROUND: Propolis has numerous biologic activities including antibiotic,
antifungal, antiviral and anti-inflammatory properties. The present work is
aimed to study the effect of crude Egyptian propolis on tumor in mice induced
by Ehrlich ascitis carcinoma (EAC) cell line. RESULTS: The administration
of propolis (160 mg/kg body weight), by gastric intubation 2 h before the
intraperitoneal injection of EAC, effectively inhibited tumor growth and the
proliferation of EAC. The tumor volume was markedly reduced from 7+/-0.9 ml
in EAC-infected mice to 1.6+/-0.95 ml in propolis-treated mice. Also, the
lipid peroxide level which was 13.3+/-1.24 nmol malodialdehyde (MDA)/mg protein
in EAC infected mice was significantly decreased to 3.3+/-2.1 nmol MDA/mg
protein. Reduced glutathione (GSH) and glutathione S-transferase (GST) concentrations
were markedly increased in propolis-treated mice. This effect was associated
with inhibition of cell cycle progression and induction of apoptosis. Administration
of propolis 2 h before injection of EAC arrested cells in G0/G1 phase and
resulted in a decrease in the viability, DNA, total RNA and protein level
of tumor cells. CONCLUSIONS: Crude Egyptian propolis has a strong inhibitory
activity against tumors. The anti-tumor mechanism may be mediated by preventing
oxidative damage and induction of apoptosis.
PMID: 14637260 [PubMed - indexed for MEDLINE]
| 35: Biochem Pharmacol. 2003 Dec 15;66(12):2281-9. |
Involvement of tumor
suppressor protein p53 and p38 MAPK in caffeic acid phenethyl ester-induced
apoptosis of C6 glioma cells.
Lee YJ, Kuo HC, Chu CY, Wang CJ, Lin WC, Tseng TH.
Department of Chemistry, National Changhua University of Education, Changhua,
Taiwan, ROC.
Caffeic acid phenethyl ester (CAPE), an active component of propolis, has
many biological and pharmacological activities including antioxidant, anti-inflammation,
antiviral action, and anticancer effect. Our previous studies showed that
CAPE exhibited significant cytotoxicity in oral cancer cells. Herein we further
investigated the cytotoxicity potential of CAPE and the mechanism of its action
in C6 glioma cells. The data exhibited that C6 glioma cells underwent internucleosomal
DNA fragmentation 24 hr after the treatment of CAPE (50 microM). The proportion
of C6 glioma cells with hypodiploid nuclei was increased to 24% at 36 hr after
the exposure. Further results showed that CAPE induced the release of cytochrome
c from mitochondria into cytosol, and the activation of CPP32. CAPE application
also enhanced the expression of p53, Bax, and Bak. Finally, the potential
signaling components underlying CAPE induction of apoptosis were elucidated.
We found that CAPE activated extracellular signal-regulated kinase (ERKs)
and p38 mitogen-activated protein kinase (p38 MAPK) in C6 glioma cells. More
importantly, p38 kinase formed a complex with p53 after the treatment of CAPE
for 0.5 hr. The expression of p53, phospho-serine 15 of p53, and Bax, and
inactivate form of CPP32 was suppressed by a pretreatment of a specific p38
MAPK inhibitor, SB203580. The resultant data suggest that p38 MAPK mediated
the CAPE-induced p53-dependent apoptosis in C6 glioma cells.
PMID: 14637186 [PubMed - indexed for MEDLINE]
| 36: Biol Pharm Bull. 2003 Jul;26(7):1057-9. |
Cell growth inhibitory
effect of cinnamic acid derivatives from propolis on human tumor cell lines.
Akao Y, Maruyama H, Matsumoto K,
Ohguchi K, Nishizawa K,
Sakamoto T, Araki Y, Mishima S, Nozawa Y.
Gifu International Institute of Biotechnology, Kakamigahara, Japan. yakao@giib.or.jp
A cell growth inhibitory effect of drupanin and baccharin, ingredients of
propolis, was found in human cancer cell lines. These compounds induced apoptosis
in the cells characterized by morphological and nucleosomal DNA fragmentation
analysis. Their effects were less potent compared with that of artepillin
C, which is a known anticancer compound from propolis. Importantly, HL60 cells
were more sensitive to drupanin than were Con A-stimulated peripheral blood
lymphocytes, whereas the potency of artepillin C was the opposite of that
of drupanin.
PMID: 12843641 [PubMed - indexed for MEDLINE]
| 37: J Nat Prod. 2003 Apr;66(4):503-6. |
Cytotoxic prenylflavanones
from Taiwanese propolis.
Chen CN, Wu CL, Shy HS, Lin JK.
Graduate Institute of Biochemistry and Molecular Biology, College of Medicine,
National Taiwan University, No. 1, Section 1, Jen-ai Road, Taipei, Taiwan
100, Republic of China.
Two new prenylflavanones, propolin A (2) and propolin B (3), were isolated
and characterized from Taiwanese propolis. Both compounds were found to have
cytotoxic properties against three cancer cell lines. DNA content analyses
and DNA fragmentation indicated that propolin A (2) efficiently induced apoptosis
in cancer cell lines, but had no effect on the cell cycle program. Furthermore,
both propolin A (2) and B (3) are potential antioxidant agents and show strong
scavenging effects against most types of free radicals.
PMID: 12713401 [PubMed - indexed for MEDLINE]
| 38: Cancer Lett. 2003 Apr 25;193(2):155-9. |
Inhibitory effects of
propolis granular A P C on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced
lung tumorigenesis in A/J mice.
Sugimoto Y, Iba Y, Kayasuga R, Kirino Y, Nishiga M, Alejandra Hossen M,
Okihara K, Sugimoto H, Yamada H, Kamei C.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University,
1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
We examined the effect of propolis granular A. P. C on lung tumorigenesis
in female A/J mice. Lung tumors were induced by the tobacco-specific carcinogen,
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) administered in drinking
water for 7 weeks in mice maintained on an AIN-76A semi-synthetic diet. Propolis
granular A. P. C (100 mg/kg body wt.) was administered orally daily for 6
days/week from 1 week before NNK administration and throughout the experiment.
Sixteen weeks after the NNK treatment, the mice were killed and the number
of surface lung tumors was measured. The number of lung tumors in mice treated
with NNK alone for 7 weeks (9.4 mg/mouse) was significantly more than in that
observed in control mice. Propolis granular A. P. C significantly decreased
the number of lung tumors induced by NNK. These results indicate that propolis
granular A. P. C is effective in suppressing NNK-induced lung tumorigenesis
in mice.
PMID: 12706872 [PubMed - indexed for MEDLINE]
| 39: J Ethnopharmacol. 2003 Feb;84(2-3):265-73. |
Immunomodulation by water-soluble
derivative of propolis: a factor of antitumor reactivity.
Orsolic N, Basic I.
Department of Animal Physiology, Faculty of Science, University of Zagreb,
Rooseveltov trg 6, 10 000 Zagreb, Croatia. norsolic@yahoo.com
The antimetastatic efficacy of a water-soluble derivative of propolis (WSDP)
was studied. Tumor was a transplantable mammary carcinoma of CBA mouse. Metastases
in the lung were generated by 2 x 10(5) viable tumor cells i.v. WSDP was given
intraperitoneally at doses of 50 or 150 mg/kg before or after tumor cell inoculation.
Therapies reduced the number of metastases in the lung and tumor growth was
suppressed significantly by WSDP. It is likely that antimetastatic activity
of the WSDP is mainly mediated by immunomodulatory activity. Changes in several
immunological parameters such as production of lymphocyte activating factor
by peritoneal macrophages and the efficacy of those macrophages to kill tumor
cell in vitro, responses of lymphocytes to mitogen, and weight and cellularity
of spleen, respectively, correlated well with antimetastatic properties of
the WSDP. Based on results we postulate that the antimetastatic activity of
propolis includes a pronounced immunomodulatory activity mainly toward augmentation
of nonspecific antitumor resistance in mice via macrophage activation. Copyright
2002 Elsevier Science Ireland Ltd.
PMID: 12648825 [PubMed - indexed for MEDLINE]
| 40: Fitoterapia. 2002 Nov;73 Suppl 1:S38-43. |
Effect of a propolis
extract and caffeic acid phenethyl ester on formation of aberrant crypt foci
and tumors in the rat colon.
Borrelli F, Izzo AA, Di Carlo G, Maffia P, Russo A, Maiello FM, Capasso F, Mascolo N.
Department of Experimental Pharmacology, University of Naples 'Federico II',
Via D. Montesano 49, 80131, Naples, Italy. franborr@unina.it
We have studied the effect of propolis and its main active ingredient caffeic
acid phenetyl ester (CAPE) on formation of aberrant crypt foci (ACF) and tumors
in the rat colon in vivo. CAPE (50 mg/kg i.p.) reduced the formation of ACF
and tumor induced by azoxymethane, while propolis ethanolic extract was without
effect. These results suggest a potential anti-carcinogenesis of CAPE but
not propolis.
PMID: 12495708 [PubMed - indexed for MEDLINE]
| 41: Cancer Biother Radiopharm. 2002 Oct;17(5):553-62. |
Antitumor and anticytopenic
effects of aqueous extracts of propolis in combination with chemotherapeutic
agents.
Suzuki I, Hayashi I, Takaki T, Groveman DS,
Fujimiya Y.
Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University
of Medical Science, Suzuka, Mie 510-0293, Japan.
Using an ICR mouse model bearing a syngeneic Ehrlich ascitis carcinoma, the
present study was undertaken to examine the effects of crude, water-soluble
propolis (CWSP) on tumor progression, chemotherapeutic efficacy, and hematopoiesis
in the peripheral blood. It was demonstrated that CWSP, administered subcutaneously,
resulted in marked regression of tumor growth in mice, at the early phase
after tumor inoculation (CWSP, p < 0.05 vs. saline control). Molecular
analysis indicated that the CWSP is composed of 8.4% protein, 4.2% quercetin
plus a variety of saccharides with a molecular weight of 29 kDa. Orally administered
CWSP did not produce any regression for the observation period (oral CWSP,
p > 0.05 vs. saline control). Peritoneal injection of CWSP into neonatal
mice resulted in an increased lymphocyte/polymorphonuclear leukocyte ratio
activity, indicating the potential activation of lymphoid cell lineages. These
observations suggest that subcutaneously injected CWSP could regulate the
development of tumors by possibly stimulating multicellular immunity. In addition,
oral administration of CWSP concurrently with 5-fluorouracil (5-FU) or mitomycin
C (MMC), significantly increased tumor regression as compared with the respective
chemotherapy alone, illustrating the adjuvant effect of orally administered
CWSP for tumor regression when combined with chemotherapeutic agents. To examine
further the potential usefulness of CWSP for chemotherapeutic regimens, which
induce profound multilineage hematopoietic suppression, mice that received
CWSP orally in addition to a 5-FU or MMC were followed for absolute numbers
of platelets and white and red blood cells. The oral administration of CWSP
significantly ameliorated the cytopenia induced by 5-FU, resulting in recovery
of white as well as red blood cell counts (5-FU plus CWSP, p < 0.05 vs.
5-FU alone or water control; white blood cells on day 15, red blood cells
on day 25), but no marked effects on platelet counts was observed (5-FU plus
CWSP, p > 0.05 vs. 5-FU alone or water control). On the other hand, CWSP
significantly reduced all three MMC-induced cytopenias, especially at the
later stage of the chemotherapeutic course (after day 30), suggesting repetitive
requirements of oral administration of CWSP. In summary, subcutaneous administration
of an aqueous CWSP resulted in marked regression of transplanted tumors. Orally
administered CWSP combined with chemotherapeutic agents significantly increased
tumor regression and ameliorated the cytopenia induced by the chemotherapeutic
agents alone. These results suggest the benefits of potential clinical trials
using CWSP combined with chemotherapeutic agents in order to maximize enhanced
immunity while potentially minimizing postchemotherapeutic deteriorated reactions.
PMID: 12470425 [PubMed - indexed for MEDLINE]
| 42: Isr Med Assoc J. 2002 Nov;4(11 Suppl):919-22. |
Comment in:
· Isr Med Assoc J. 2002 Nov;4(11 Suppl):944-6.
The effect of herbal remedies
on the production of human inflammatory and anti-inflammatory cytokines.
Barak V, Birkenfeld S,
Halperin T, Kalickman I.
Immunology Laboratory for Tumor Diagnosis, Department of Oncology, Hadassah
University Hospital, Jerusalem, Israel. barak845@yahoo.com
BACKGROUND: Some herbal remedies are sold as food additives and are believed
to have immune-enhancing properties. OBJECTIVES: To study the effect of five
herbal remedies--Sambucol Black Elderberry Extract, Sambucol Active Defense
Formula and Sambucol for Kids (with known antiviral properties), Protec and
Chizukit N (containing propolis and Echinacea, claimed to be immune enhancers)--on
the production of cytokines, one of the main components of the immune system.
METHODS: The production of four inflammatory cytokines (interleukin-1 beta,
tumor necrosis factor alpha, and IL-6 and IL-8) and one anti-inflammatory
cytokine (IL-10) was tested using blood-derived monocytes from 12 healthy
donors. RESULTS: The Sambucol preparations increased the production of five
cytokines (1.3-6.2 fold) compared to the control. Protec induced only a moderate
production of IL-8 (1.6 fold) and IL-10 (2.3 fold) while Chizukit N caused
only a moderate increase in IL-10 production (1.4 fold). Both Protec and Chizukit
N caused moderate decreases in IL-1 beta, TNF alpha and IL-6 production. Lipopolysaccharide,
a known activator of monocytes, induced the highest levels of cytokine production
(3.6-10.7 fold). CONCLUSIONS: The three Sambucol formulations activate the
healthy immune system by increasing inflammatory and anti-inflammatory cytokines
production, while the effect of Protec and Chizukit N is much less. Sambucol
could therefore have immunostimulatory properties when administered to patients
suffering from influenza (as shown before), or immunodepressed cancer or AIDS
patients who are receiving chemotherapy or other treatments.
PMID: 12455180 [PubMed - indexed for MEDLINE]
| 43: J Ethnopharmacol. 2002 Oct;82(2-3):89-95. |
Estrogenic effects of
ethanol and ether extracts of propolis.
Song YS, Jin C, Jung KJ, Park EH.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science
and Technology, P.O. Box 131, Cheongryang, Seoul, South Korea.
Propolis obtained from honeybee hives has been used in Oriental folk medicine
as an anti-inflammatory, anti-carcinogenic, or immunomodulatory agent. The
potential estrogenic activity of propolis was investigated in vitro using
the MCF-7 human breast cancer cell proliferation, human estrogen receptor
(hER) binding and yeast-based steroid receptor transcription, and in vivo
using the immature rat uterotrophic effect. Treatments with ethanol extract
of propolis (EEP) and ether extract of propolis (REP) enhanced MCF-7 cell
proliferation in concentrations ranging from 0.8 to 4 microg/ml. Both EEP
and REP competed for binding of [3H]17beta-estradiol to the hER with IC(50)
values of 9.14 and 9.72 microg/ml, respectively. In yeast estrogen receptor
transcription assay, both EEP and REP were found to be estrogenic with EC(50)
values of 9.48, and 8.55 microg/ml, respectively. Animals treated with EEP
or REP for 4 days (500-1000 mg/kg per day, s.c.) exhibited significant dose-dependent
increases in uterine wet weight. However, in the yeast androgen and progesterone
receptor transcription assays, either EEP or REP was found not to be active.
The results suggest that propolis produces estrogenic effects through activation
of estrogen receptors.
PMID: 12241982 [PubMed - indexed for MEDLINE]
| 44: Z Naturforsch [C]. 2002 Mar-Apr;57(3-4):372-8. |
Polyisoprenylated benzophenones
in cuban propolis; biological activity of nemorosone.
Cuesta-Rubio O,
Frontana-Uribe BA,
Ramirez-Apan T,
Cardenas J.
Instituto de Farmacia y Alimentos, Universidad de la Habana, Cuba.
The Copey tree (Clusia rosea) has a large distribution in Cuba and its floral
resin is a rich source of polyisoprenylated benzophenones. To determine the
presence of these natural products, we carried out a study by HPLC of 21 propolis
samples produced by honey bees (Apis mellifera) from different provinces of
Cuba. Nemorosone resulted to be the most abundant polyisoprenylated benzophenone
and the mixture of xanthochymol and guttiferone E was also observed, but in
minor proportion. We studied the biological activity of the pure natural product
nemorosone and its methyl derivatives. We found that nemorosone has cytotoxic
activity against epitheloid carcinoma (HeLa), epidermoid carcinoma (Hep-2),
prostate cancer (PC-3) and central nervous system cancer (U251). It also exhibited
antioxidant capacity. Methylated nemorosone exhibited less biological activity
than the natural product.
PMID: 12064743 [PubMed - indexed for MEDLINE]
| 45: J Nat Prod. 2002 May;65(5):673-6. |
Constituents of Chinese
propolis and their antiproliferative activities.
Usia T, Banskota AH,
Tezuka Y, Midorikawa K,
Matsushige K,
Kadota S.
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University,
2630-Sugitani, Toyama 930-0194, Japan.
Two new flavonoids, 3-O-[(S)-2-methylbutyroyl]pinobanksin (1) and 6-cinnamylchrysin
(2), were isolated from the EtOAc-soluble fraction of the MeOH extract of
Chinese propolis, along with 12 known compounds (3-14). The structures of
the isolated compounds were elucidated on the basis of spectroscopic and chemical
analyses. The isolated compounds were tested for their antiproliferative activity
toward five different cancer cell lines. Benzyl caffeate (13) and phenethyl
caffeate (14) showed potent antiproliferative activity toward tested cell
lines with a selective activity toward colon 26-L5 carcinoma cell line (EC(50)
values: 13, 1.01; 14, 0.30 microM).
PMID: 12027739 [PubMed - indexed for MEDLINE]
| 46: Teratog Carcinog Mutagen. 2002;22(3):183-94. |
Protective action of
propolis on the rat colon carcinogenesis.
Bazo AP, Rodrigues MA,
Sforcin JM, de Camargo JL,
Ribeiro LR, Salvadori DM.
Departamento de Patologia, Faculdade de Medicina, UNESP, Botucatu, Sao Paulo,
Brazil.
Propolis is a honeybee product with several biological and therapeutical properties.
Its effect on the process of colon carcinogenesis and DNA damage were evaluated
in the male Wistar rats using the aberrant crypt foci (ACF) assay and the
comet assay, respectively. For both tests, animals were treated with the colon
carcinogen 1,2 dimethylhydrazine (DMH, 40 mg/kg, s.c.) for 2 weeks (two injections/week)
in order to induce both DNA damage and ACF. The animals were divided into
groups that received propolis (ethanolic extract) at three different doses
(10, 30, and 90 mg/kg b.w., by gavage), either simultaneously or after DMH
treatment. For the comet assay, peripheral blood samples were collected 4
h after the last DMH treatment. All animals were sacrificed at the 5th week
for evaluation of ACF. The results show that only the intermediate dose (30
mg/kg) of propolis, administered after DMH initiation, is significantly associated
to a smaller number of aberrant crypts in the distal colon. No effect on DNA
damage in peripheral blood cells, however, was verified by the comet assay.
These data suggest that propolis has a protective influence on the process
of colon carcinogenesis, suppressing the development of preneoplastic lesions,
and probably exerts no protection against the initiation of carcinogenesis.
Copyright 2002 Wiley-Liss, Inc.
PMID: 11948629 [PubMed - indexed for MEDLINE]
| 47: J Ethnopharmacol. 2002 Apr;80(1):67-73. |
Antiproliferative activity
of the Netherlands propolis and its active principles in cancer cell lines.
Banskota AH,
Nagaoka T, Sumioka LY, Tezuka Y, Awale S, Midorikawa K,
Matsushige K,
Kadota S.
Department of Natural Products Chemistry, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, 2630-Sugitani, 930-0194, Toyama, Japan.
The MeOH extract of the Netherlands propolis showed promising antiproliferative
activity toward highly liver-metastatic murine colon 26-L5 carcinoma with
an EC(50) value of 3.5 microg/ml. Further, antiproliferative activity-guided
purification of the MeOH extract led us to isolate four flavonoids (1-4),
seven cinnamic acid derivatives (5-11) and two new glycerol derivatives (12,
13), whose structures were elucidated on the basis of spectral analysis. The
isolated compounds were tested for their antiproliferative activity against
murine colon 26-L5, murine B16-BL6 melanoma, human HT-1080 fibrosarcoma and
human lung A549 adenocarcinoma cell lines. The benzyl (9), phenethyl (10)
and cinnamyl caffeates (11) possessed potent antiproliferative activities
with EC(50) values of 0.288, 1.76 and 0.114 microM, respectively, toward colon
26-L5 carcinoma. These caffeates were considered to be active constituents
of the Netherlands propolis in their antiproliferative activity. The antioxidative
activity of these caffeates may play an important role in their antiproliferative
activities.
PMID: 11891088 [PubMed - indexed for MEDLINE]
| 48: Cancer Lett. 2002 Jan 10;175(1):53-61. |
Caffeic acid phenethyl
ester inhibits nitric oxide synthase gene expression and enzyme activity.
Song YS, Park EH, Hur GM, Ryu YS, Lee YS, Lee JY, Kim YM, Jin C.
Bioanalysis and Biotransformation Research Center, Korea Institute of Science
and Technology, P.O. Box 131, Cheongryang, 130-650, Seoul, South Korea.
Since nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS)
has been known to be involved in inflammatory and autoimmune-mediated tissue
destruction, modulation of NO synthesis or action represents a new approach
to the treatment of inflammatory and autoimmune diseases. Caffeic acid phenethyl
ester (CAPE), an active component of honeybee propolis, has been identified
to show anti-inflammatory, anti-viral and anti-cancer activities. The present
study, therefore, examined effects of CAPE on iNOS expression and activity
of iNOS enzyme itself. Treatment of RAW 264.7 cells with CAPE significantly
inhibited NO production and iNOS protein expression induced by lipopolysaccharide
(LPS) plus interferon-gamma (IFN-gamma). CAPE also inhibited iNOS mRNA expression
and nuclear factor-kappa B (NF-kappaB) binding activity in a concentration-dependent
manner. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked
to a chloramphenicol acetyltransferase reporter gene, revealed that CAPE inhibited
the iNOS promoter activity induced by LPS plus IFN-gamma through the NF-kappaB
sites of the iNOS promoter. In addition, CAPE directly interfered with the
catalytic activity of murine recombinant iNOS enzyme. These results suggest
that CAPE may exert its anti-inflammatory effect by inhibiting the iNOS gene
expression at the transcriptional level through the suppression of NF-kappaB
activation, and by directly inhibiting the catalytic activity of iNOS.
PMID: 11734336 [PubMed - indexed for MEDLINE]
| 49: Arch Virol. 2001 Aug;146(8):1517-26. |
Effect of propolis extract
on malignant cell transformation by moloney murine sarcoma virus.
Huleihel M, Ishano V.
The Institute for Applied Biosciences, Ben-Gurion University of the Negev,
Beer-Sheva, Israel. mahmoudh@bgumail.bgu.ac.il
An aqueous extract of propolis was found to significantly inhibit NIH/3T3
cell malignant transformation by Moloney murine sarcoma virus (MuSV-124).
The inhibitory effect of propolis extract was most effective when it was added
2 h before infection or at the time of infection. The continuous presence
of propolis extract in the culture medium was essential for full prevention
of malignant cell transformation. When treatment with propolis extract was
terminated, five to ten days post-infection, there was a significant recovery
in cell transformation. These results suggest that propolis extract inhibits
a late step after provirus integration into the host genome. Addition of propolis
extract after infection with MuSV significantly inhibited cell transformation.
The inhibitory effect of propolis appeared to be the result of the inhibition
of primary--not secondary--infections, since MuSV-124 yields a virus-nonproducing
infection.
PMID: 11676414 [PubMed - indexed for MEDLINE]
| 50: Anticancer Res. 2001 May-Jun;21(3B):1665-71. |
PM-
Luo J, Soh JW, Xing WQ, Mao Y, Matsuno T, Weinstein IB.
Herbert Irving Comprehensive Cancer Center, Columbia Presbyterian Medical
Center, College of Physicians and Surgeons, Columbia University, New York,
NY 10032, USA.
Propolis has numerous biologic activities including antibiotic, antifungal,
antiviral and anti-inflammatory properties. Several components isolated from
propolis have been shown to have anticancer activity. This study demonstrates
that the compound PM-3 (3-[2-dimethyl-8-(3-methyl-2-butenyl)benzopyran]-6-propenoic
acid) isolated from Brazilian propolis markedly inhibits the growth of MCF-7
human breast cancer cells. This effect was associated with inhibition of cell
cycle progression and induction of apoptosis. Treatment of MCF-7 cells with
PM-3 arrested cells in the G1 phase and resulted in a decrease in the protein
levels of cyclin D1 and cyclin E. PM-3 also inhibited the expression of cyclin
D1 at the transcriptional level when examined in cyclin D1 promoter luciferase
assays. Induction of apoptosis by PM-3 occurred within 48 hours after treatment
of MCF-7 cells. The MCF-7 treated cells also displayed a decrease in the level
of the estrogen receptor (ER) protein and inhibition of estrogen response
element (ERE) promoter activity. Therefore, PM-3 merits further investigation
with respect to breast cancer chemoprevention or therapy.
PMID: 11497245 [PubMed - indexed for MEDLINE]
| 51: Mol Carcinog. 2001 Jun;31(2):83-9. |
Suppression of cell transformation
and induction of apoptosis by caffeic acid phenethyl ester.
Nomura M, Kaji A, Ma W, Miyamoto K, Dong Z.
Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of
honeybee hives, has been shown to block tumor promotion and to have toxic
effects on several cancer cells. The mechanism of the anti-tumor promotion
activity of CAPE is unclear, however. In this study, we found that CAPE suppressed
12-O-tetradecanoylphorbol-13-acetate-induced cell transformation and induced
apoptosis in mouse epidermal JB6 Cl 41 cells. No difference in induction of
apoptosis was observed between normal lymphoblasts and sphingomyelinase-deficient
cell lines. Although CAPE treatment of two p53 mutant tumor cell lines, NCI-H358
and SK-OV-3, and p53-deficient (p53(-/-)) cells caused the cleavage of caspase-3
as well as DNA fragmentation, caspase-3 cleavage was seen early (at 6 h) only
in cells expressing wild-type p53 (p53(+/+)) and Cl 41 cells. These results
suggested that p53 may be involved in the early stage of CAPE-induced apoptosis.
The p53-dependent transcription activation occurred 2 h after treatment with
CAPE and reached a maximum at 6 h in Cl 41 p53 DNA-binding sequence stable
transfectant cells. In addition, phosphorylation of p53 at serine 15 and serine
392 was induced in Cl 41 cells within 6 h after treatment with CAPE. Therefore,
CAPE may induce apoptosis through p53-dependent and p53-independent pathways
and its anti-tumor promotion activity may have occurred through the induction
of apoptosis. Copyright 2001 Wiley-Liss, Inc.
PMID: 11429785 [PubMed - indexed for MEDLINE]
| 52: Mutat Res. 2001 May;488(2):135-50. |
Anti-genotoxicity of
galangin as a cancer chemopreventive agent candidate.
Heo MY, Sohn SJ, Au WW.
College of Pharmacy, Kangwon National University, Chunchon 200, South Korea.
h0858my@hanmail.net
Flavonoids are polyphenolic compounds that are present in plants. They have
been shown to possess a variety of biological activities at non-toxic concentrations
in organisms. Galangin, a member of the flavonol class of flavonoid, is present
in high concentrations in medicinal plants (e.g. Alpinia officinarum) and
propolis, a natural beehive product. Results from in vitro and in vivo studies
indicate that galangin with anti-oxidative and free radical scavenging activities
is capable of modulating enzyme activities and suppressing the genotoxicity
of chemicals. These activities will be discussed in this review. Based on
our review, galangin may be a promising candidate for cancer chemoprevention.
Publication Types:
· Review
PMID: 11344041 [PubMed - indexed for MEDLINE]
| 53: Virchows Arch. 2001 Mar;438(3):259-70. |
Pulmonary carcinogenesis
induced by ferric nitrilotriacetate in mice and protection from it by Brazilian
propolis and artepillin C.
Kimoto T, Koya-Miyata S,
Hino K, Micallef MJ,
Hanaya T, Arai S, Ikeda M, Kurimoto M.
Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki 675-1,
Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp
In experiments using the renal carcinogen ferric nitrilotriacetate (Fe-NTA)
in male ddY mice, primary pulmonary cancers were also induced in bronchiolar
and alveolar tissues. 4-Hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine
(8-OHdG), products of oxidative processes, increased in bronchiolar and alveolar
cells after administration of Fe-NTA. These substances disappeared after oral
administration of propolis or artepillin C, as shown histochemically, and
correlated with an anticancer prophylactic effect of propolis and artepillin
C. From our investigation, lipid peroxidation seems to play an important role
in pulmonary carcinogenesis. Malignant progression from adenoma of bronchiolar
or alveolar origin to malignant tumors has been proposed to involve a stepwise
transformation. In our study, adenomas developed into adenocarcinomas and
large cell carcinomas after treatment with Fe-NTA. In contrast, after oral
administration of propolis or artepillin C, adenomas did not progress to carcinomas.
Instead of developing into large cell cancers, as induced by Fe-NTA in control
mice, adenomas showed remarkable proliferation of macrophages and local anti-oxidant
activity after treatment with either propolis or artepillin C. Propolis and
artepillin C therefore appear to inhibit lipid peroxidation and the development
of pulmonary cancers.
PMID: 11315623 [PubMed - indexed for MEDLINE]
| 54: Anticancer Res. 2001 Jan-Feb;21(1A):221-8. |
Apoptosis of human leukemia
cells induced by Artepillin C, an active ingredient of Brazilian propolis.
Kimoto T, Aga M, Hino K, Koya-Miyata S,
Yamamoto Y, Micallef MJ,
Hanaya T, Arai S, Ikeda M, Kurimoto M.
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Fujisaki 675-1,
Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp
Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is an active ingredient
of Brazilian propolis that possesses anti-tumor activity. When Artepillin
C was applied to human leukemia cell lines of different phenotypes, namely,
lymphocytic leukemia (7 cell lines of T-cell, 5 cell lines of B-cell), myeloid
and monocytic leukemia and non-lymphoid non-myeloid leukemia cell lines in
vitro, Artepillin C exhibited potent cytocidal effects and induced marked
levels of apoptosis in all the cell lines. The most potent effects were observed
in the T-cell lines. Apoptotic bodies and DNA fragmentation were induced in
the cell lines after exposure to Artepillin C. DNA synthesis in the leukemia
cells was clearly inhibited and disintegration of the cells was confirmed
microscopically. Apoptosis of the leukemia cells may be partially associated
with enhanced Fas antigen expression and loss of mitochondrial membrane potential.
In contrast, although Artepillin C inhibited the growth of pokeweed mitogen
(PWM)-stimulated normal blood lymphocytes, it was not cytocidal to normal
unstimulated lymphocytes. These results suggested that Artepillin C, an active
ingredient of Brazilian propolis, has anti-leukemic effects with limited inhibitory
effects on normal lymphocytes.
PMID: 11299738 [PubMed - indexed for MEDLINE]
| 55: In Vivo. 2001 Jan-Feb;15(1):17-23. |
Diverse biological activities
of healthy foods.
Kobayashi N,
Unten S, Kakuta H, Komatsu N, Fujimaki M, Satoh K, Aratsu C, Nakashima H,
Kikuchi H, Ochiai K, Sakagami H.
Fujimi Bee House, Shiki, Saitama, Japan.
Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented
sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil
(extracted by super critical state (40 degrees C, 350 atmospheric pressure))]
were investigated. The pine needle, sesame and powdered coffee was also extracted
successively by ethanol and hot water, and lyophilized. The pine needle and
coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal
and oxidation activity, as compared with other 4 lipophilic healthy foods.
However, propolis showed slightly lower, but significant cytotoxic and bactericidal
activity with much reduced oxidation potential. ESR spectroscopy demonstrated
that the cytotoxic activity of these extracts was closely related to their
radical generation and O2- scavenging activities. Healthy food components
may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice
with pine needle, sesame or powdered coffee extract significantly reduced
the lethality of bacterial infection, possibly due to their host-mediated
action. These extracts failed to reduce the cytophatic effect of HIV-1 (human
immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity
was detected in mice by oral administration of 10 g/kg of these extracts.
This data suggest the medicinal efficacy of healthy foods.
PMID: 11286123 [PubMed - indexed for MEDLINE]
| 56: Nutr Cancer. 2000;37(2):179-86. |
Modifying effects of propolis
on MeIQx promotion of rat hepatocarcinogenesis and in a female rat two-stage
carcinogenesis model after multiple carcinogen initiation.
Kawabe M, Lin C, Kimoto N, Sano M, Hirose M, Shirai T.
First Department of Pathology, Nagoya City University Medical School, Nagoya
467-8601, Japan.
The modifying effects of the dietary administration of water- and ethanol-extracted
propolis produced in Brazil (WB and EB, respectively) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
(MeIQx) promotion of rat hepatocarcinogenesis were investigated in a medium-term
liver bioassay system with use of male Fischer 344 rats. The number and area
of glutathione S-transferase placental form (GST-P)-positive foci in rats
given 0.5% WB were significantly increased compared with the group given MeIQx
alone. Furthermore, the numbers of GST-P-positive foci were higher in rats
given 0.1% WB or EB than in those given the basal diet alone. The modifying
effects of propolis on other organs were also examined in female Fischer 344
rats given multiple carcinogens for initiation. Rats received water- and ethanol-extracted
propolis produced in Brazil and Uruguay (WB, EB, WU, and EU, respectively)
in the diet after exposure to three different carcinogens. The incidence of
total mammary tumors was significantly lower in rats given EU than in the
control group. These results indicate that a water extract of propolis exerts
a cocarcinogenic effect on MeIQx hepatocarcinogenesis while promoting the
effect at low dose in a two-stage hepatocarcinogenesis model. Moreover, they
suggest that ethanol-extracted propolis may be an inhibitor of mammary gland
carcinogenesis.
PMID: 11142091 [PubMed - indexed for MEDLINE]
| 57: Pathol Int. 2000 Sep;50(9):679-89. |
Renal carcinogenesis
induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian
propolis and artepillin C.
Kimoto T, Koya S, Hino K, Yamamoto Y, Nomura Y, Micallef MJ,
Hanaya T, Arai S, Ikeda M, Kurimoto M.
Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki, Okayama,
Japan.
The protective effect of Brazilian propolis and its extract Artepillin C against
ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis
was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads
to a high incidence of renal cell carcinoma (RCC) in mice. Administration
of propolis by gastric intubation 2 h before or Artepillin C at either the
same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg
Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated
from the measurement of renal thiobarbituric acid-reactive substances (TBARS)
or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins
and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10
mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused
subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear
cells in the renal proximal tubules, and gave rise to RCC 12 months later.
A protective effect from carcinogenicity was observed in mice given propolis
or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple
cysts composed of precancerous lesions with multilayered and proliferating
large atypical cells. Mice treated with propolis and Artepillin C also had
cysts, but these were dilated and composed of flat cells. These results suggest
that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis
induced by Fe-NTA in mice.
PMID: 11012980 [PubMed - indexed for MEDLINE]
| 58: Cancer Lett. 2000 Aug 31;157(1):31-8. |
Restoration of gap junctional
intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed
rat liver epithelial cell line.
Na HK, Wilson MR, Kang KS, Chang CC, Grunberger D,
Trosko JE.
Department of Pediatrics and Human Development, National Food Safety and Toxicology
Center, Michigan State University, East Lansing 48824-1317, USA.
Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis,
has been identified as having anti-inflammatory, anti-viral and anti-cancer
properties. Since the deficiency of gap junctional intercellular communication
(GJIC) has been shown to be a characteristic of most cancer cells, this study
was designed to test the hypothesis that the anti-carcinogenic activity of
CAPE might be related to its ability to restore GJIC in tumorigenic GJIC-deficient
cells (WB-ras2 cells). The results showed that CAPE restored GJIC, phosphorylation
of connexin 43 (Cx43) and its normal localization on the plasma membrane in
WB-ras2 cells after 3 days at 5 microg/ml concentration. Additionally, CAPE
inhibited growth in soft agar and decreased the protein level of p21(ras).
The results are consistent with the hypothesis that the anti-cancer mechanism
of CAPE may be mediated by its ability to restore GJIC.
PMID: 10893439 [PubMed - indexed for MEDLINE]
| 59: Cancer Lett. 1999 Dec 1;147(1-2):221-7. |
Post-initiation effects of a
super critical extract of propolis in a rat two-stage carcinogenesis model
in female F344 rats.
Kimoto N, Hirose M, Kawabe M, Satoh T, Miyataka H, Shirai T.
First Department of Pathology, Nagoya City University Medical School, Nagoya,
Japan.
Post-initiation modifying effects of dietary administration of a super critical
extract of propolis on major organs were examined using a two-stage carcinogenesis
model. Groups of 21 or 22 F344 female rats were treated sequentially with
2,2'-dihydroxy-di-n-propylnitrosamine (DHPN, i.g.), 7,12-dimethylbenz[a]anthracene
(DMBA, i.g.), 1,2-dimethylhydrazine (DMH, s.c.) and N-butyl-N-(4-hydroxybutyl)nitrosamine
(BBN, in drinking water) during the first 3 weeks for initiation, and then
administered diet containing 0.1 or 0.01% propolis for 33 weeks. Further groups
were treated with the carcinogens alone, 0.1% propolis alone or basal diet
alone. All surviving animals were killed at week 36, and major organs were
examined histopathologically for development of preneoplastic and neoplastic
lesions. The incidence and multiplicity of mammary carcinomas were significantly
decreased by the 0.1 and 0.01% propolis treatments. In the urinary bladder,
the incidence of PN hyperplasia but not tumors was, in contrast, significantly
increased by 0.1% propolis. Similarly, the number and area of glutathione
S-transferase placental form (GST-P)-positive liver foci were significantly
elevated with this high dose. The results indicate that a low dose of a super
critical extract of propolis may find application as a potent chemopreventor
of mammary carcinogenesis.
PMID: 10660110 [PubMed - indexed for MEDLINE]
| 60: Int J Mol Med. 1999 Jul;4(1):29-32. |
Apoptosis induced by propolis
in human hepatocellular carcinoma cell line.
Choi YH, Lee WY, Nam SY, Choi KC, Park YE.
Department of Pathology, Chun-Chon Sacred Heart Hospital, Hallym University,
Chun-Chon city, Kang Won-Do 200-060, Korea.
Propolis has been reported to exhibit a wide spectrum of activities including
antibiotic, antiviral, anti-inflammatory, immunostimulatory and tumor carcinostatic
properties. We showed propolis induced apoptosis in a human hepatoma cell
line (SNU449) by FITC-Annexin V/PI staining. We also compared the apoptosis
inducing effect between Korean and Commercial (Sigma # p-1010) propolis. There
was no difference on apoptosis between them.
PMID: 10373633 [PubMed - indexed for MEDLINE]
| 61: Cancer Detect Prev. 1998;22(6):506-15. |
Apoptosis and suppression of
tumor growth by artepillin C extracted from Brazilian propolis.
Kimoto T, Arai S, Kohguchi M, Aga M, Nomura Y, Micallef MJ,
Kurimoto M, Mito K.
Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan.
Artepillin C was extracted from Brazilian propolis. Artepillin C (3,5-diprenyl-4-hydroxycinnamic
acid) has a molecular weight of 300.40 and possesses antibacterial activity.
When artepillin C was applied to human and murine malignant tumor cells in
vitro and in vivo, artepillin C exhibited a cytotoxic effect and the growth
of tumor cells was clearly inhibited. The artepillin C was found to cause
significant damage to solid tumor and leukemic cells by the MTT assay, DNA
synthesis assay, and morphological observation in vitro. When xenografts of
human tumor cells were transplanted into nude mice, the cytotoxic effects
of artepillin C were most noticeable in carcinoma and malignant melanoma.
Apoptosis, abortive mitosis, and massive necrosis combined were identified
by histological observation after intratumor injection of 500 microg of artepillin
C three times a week. In addition to suppression of tumor growth, there was
an increase in the ratio of CD4/CD8 T cells, and in the total number of helper
T cells. These findings indicate that artepillin C activates the immune system,
and possesses direct antitumor activity.
PMID: 9824373 [PubMed - indexed for MEDLINE]
| 62: Z Naturforsch [C]. 1997 Sep-Oct;52(9-10):702-4. |
Isolation and characterization
of cytotoxic diterpenoid isomers from propolis.
Matsuno T, Matsumoto Y,
Saito M, Morikawa J.
National Institute of Health, Tokyo, Japan.
The methanol extract of Brazilian propolis was fractionated by HPLC, based
on HuH13 (human hepatocellular carcinoma) cell cytotoxicity assay. Two isomers
of diterpenoid with a molecular formula of C20H30O3 (MW: 318.46) were isolated.
The structures of these colorless compounds were determined as clerodane diterpenoids
(I, 15-oxo-3, 13Z-kolavadien-17-oic acid; II, 15-oxo-3Z, 13E-kolavadien-17-oic
acid).
PMID: 9374000 [PubMed - indexed for MEDLINE]
| 63: Pflege Z. 1997 Mar;50(3):98-102. |
[Healing naturally with propolis.
With bee propolis to new health]
[Article in German]
Weichselgartner-Schroder
C.
PMID: 9155449 [PubMed - indexed for MEDLINE]
| 64: Gan To Kagaku Ryoho. 1996 Nov;23(13):1855-9. |
[Cell cycle and apoptosis in
cancer induced by the artepillin C extracted from Brazilian propolis]
[Article in Japanese]
Kimoto T, Arai S, Aga M, Hanaya T, Kohguchi M, Nomura Y, Kurimoto M.
Fujisaki Institute, Hayashibara Biochemical Labs., Inc.
PMID: 8937499 [PubMed - indexed for MEDLINE]
| 65: Anticancer Res. 1996 Sep-Oct;16(5A):2669-72. |
Effects of a new clerodane diterpenoid
isolated from propolis on chemically induced skin tumors in mice.
Mitamura T, Matsuno T, Sakamoto S, Maemura M, Kudo H, Suzuki S, Kuwa K, Yoshimura S,
Sassa S, Nakayama T, Nagasawa H.
Medical Research Institute, Tokyo Medical and Dental University, Japan.
Propolis is a resinous material gathered by honey bees from the buds and bark
of certain trees and plants, and used inside their hives. Characteristic components
of propolis are many kinds of flavonoid aglycones. The methanol extract of
a Brazilian propolis was fractionated by HPLC, and a tumoricidal substance
was isolated and characterized as a new clerodane diterpenoid (PMS-1) with
a molecular formula of C20H32O3 (MW: 320). We investigated the effects of
PMS-1 on skin tumorigenesis and the development of skin tumors induced by
7,12-dimethylbenz(a)anthracene application on mouse back skin. It was tentatively
concluded that PMS-1 reduced the incidence of skin tumors by inhibition of
DNA synthesis in a de novo pathway, and suppressed the growth of the tumors
by decreasing DNA synthesis in a salvage pathway.
PMID: 8917367 [PubMed - indexed for MEDLINE]
| 66: Carcinogenesis. 1996 Apr;17(4):761-5. |
Inhibitory effects of caffeic
acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced
tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in
HeLa cells.
Huang MT, Ma W, Yen P, Xie JG, Han J, Frenkel K, Grunberger D,
Conney AH.
Department of Chemical Biology, College of Pharmacy, Rutgers, State University
of New Jersey, Piscataway 08855-0789, USA.
Topical application of caffeic acid phenethyl ester (CAPE), a constituent
of the propolis of honeybee hives, to the backs of CD-1 mice previously initiated
with 7,12-dimethylbenz inverted question marka inverted question markanthracene
(DMBA) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor
promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal
DNA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mice previously
initiated with 200 nmol of DMBA resulted in 18.8 skin papillomas per mouse.
Topical application of 1, 10, 100 or 3000 nmol of CAPE together with 5 nmol
of TPA twice a week for 20 weeks inhibited the number of skin papillomas per
mouse by 24, 30, 45 or 70%, respectively, and tumor size per mouse was decreased
by 42, 66, 53 or 74%, respectively. Topical application of 5 nmol of TPA twice
weekly for 20 weeks to mice previously initiated with DMBA produced an average
of 12.6 HMdU residues per 10(4) normal bases in epidermal DNA. Topical application
of 1, 10, 100 or 3000 nmol of CAPE with 5 nmol of TPA twice weekly for 20
weeks to DMBA-initiated mice decreased the level of HMdU in epidermal DNA
by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 microM CAPE to
cultured HeLa cells inhibited the synthesis of DNA by 32, 44, 66, 79 or 95%,
respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%,
respectively, and the synthesis of protein was inhibited by 29, 30, 37, 32
or 47%, respectively. The results indicate a potent inhibitory effect of CAPE
on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of
mouse skin as well as an inhibitory effect of CAPE on the synthesis of DNA,
RNA and protein in culture HeLa cells.
PMID: 8625488 [PubMed - indexed for MEDLINE]
| 67: Anticancer Res. 1995 Sep-Oct;15(5B):1841-8. |
Apoptosis mediates the selective
toxicity of caffeic acid phenethyl ester (CAPE) toward oncogene-transformed
rat embryo fibroblast cells.
Su ZZ, Lin J, Prewett M, Goldstein NI,
Fisher PB.
Department of Pathology, Columbia University, College of Physicians and Surgeons,
New York, New York 10032, USA.
The active component of the folk medicine propolis, caffeic acid phenethyl
ester (CAPE), displays selective toxicity toward cloned rat embryo fibroblast
(CREF) cells transformed by a spectrum of diverse acting oncogenes. Identification
of the mode of action of CAPE should provide useful information for possible
applications of this compound for cancer therapy. The present study uses a
series of oncogene transformed, oncogene-reverted and CAPE-resistant oncogene
transformed CREF cells to investigate the mechanism underlying the increased
sensitivity of transformed cells to CAPE. A direct relationship exists between
the cytotoxic effects of CAPE and the induction of DNA fragmentation and apoptosis.
DNA degradation into nucleosomal fragments and apoptotic shifts in DNA cell
cycle profiles occur in CAPE-treated CREF cells transformed by wild-type 5
adenovirus (Ad5), a mutant Ad5 (H5hr1), the wild-type Ad5 E1A transforming
gene, v-src, Ha-ras and the human papilloma virus type 18 transforming genes
(HPV-18). In contrast, untransformed CREF cells, human fibroblast expression
library-induced morphological revertants of Ad5- and v-src-transformed CREF
cells, and Krev-1 expressing revertant Ha-ras-transformed CREF cells are resistant
to CAPE-induced toxicity and apoptosis. Similarly, mutant Ad5-transformed
CREF cells selected by step-wise growth in increasing concentrations of CAPE
are resistant to growth inhibition and apoptosis induced by CAPE. These findings
indicate that expression of the transformed phenotype by rodent cells evokes
sensitivity to CAPE induced toxicity through apoptosis. The acquisition of
CAPE sensitivity in rodent cells is independent of the mode of action of the
oncogenic agent. CAPE may prove useful as an antiproliferative agent in cancer
cells transformed by mechanistically diverse acting oncogenes.
PMID: 8572568 [PubMed - indexed for MEDLINE]
| 68: Cancer Res. 1995 Aug 15;55(16):3576-83. |
Apoptosis and altered redox
state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast
cells.
Chiao C, Carothers AM,
Grunberger D,
Solomon G, Preston GA, Barrett JC.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental
Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of
bee hives, was shown previously to block tumor promoter- and carcinogen-generated
oxidative processes in several assays and to engender differential toxicity
to some transformed cells. To study the mechanisms of CAPE-induced differential
cytotoxicity, nontumorigenic rat embryo fibroblasts (CREF) and adenovirus
(type 5)-transformed CREF cells (Wt3A) were used. As shown by nucleosomal-length
DNA degradation, morphological alterations by electron microscopy, in situ
labeling of 3'-OH ends, and the appearance of a hypodiploid cell population
by bivariant flow cytometry, cell death induced by CAPE in the transformed
Wt3A cells was apoptosis. Under the same CAPE treatment conditions, CREF cells
transiently growth arrested. Both CREF and Wt3A cells were radioresistant,
suggesting deficiencies in the proteins controlling the G1 checkpoint. To
explore possible mechanisms of CAPE-induced apoptosis, it was determined whether
CAPE-induced toxicity was influenced by the redox state of the cells. Depletion
of cellular glutathione (GSH) with buthionine sulfoximine before CAPE treatment
caused CREF sensitive to CAPE-induced cell death. GSH levels were also determined
in CAPE-treated CREF and Wt3A cells. The GSH level in the CREF cells was unaffected
by CAPE, whereas the Wt3A cells showed a significant reduction. When the GSH
levels were increased in Wt3A cells by treatment with the reducing agent,
N-acetyl-cysteine before CAPE treatment, the Wt3A cells were partially rescued.
Furthermore, Bcl2, which protects cells from oxidative stress, had a protective
effect against CAPE-induced apoptosis in Wt3A cells. Finally, the sensitivity
of Wt3A cells to a known oxidant, hydrogen peroxide (H2O2), was examined.
Wt3A cells were killed by H2O2-induced apoptosis, whereas CREF cells remained
resistant. When Wt3A cells were treated with catalase, a cellular enzyme that
inactivates H2O2, CAPE-induced apoptosis in Wt3A cells was reduced, further
proving that Wt3A cells were more sensitive than CREF cells to oxidative stress.
These results suggest that CAPE can modulate the redox state of cells. Sensitivity
of cells to CAPE-induced cell death may be determined by the loss of normal
redox state regulation in transformed cells.
PMID: 7543016 [PubMed - indexed for MEDLINE]
| 69: Cancer Res. 1995 Jun 1;55(11):2310-5. |
Chemoprevention of colon carcinogenesis
by phenylethyl-3-methylcaffeate.
Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS.
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla,
New York 10595, USA.
Previous studies from this laboratory have established that caffeic acid esters
present in propolis, a natural resin produced by honey bees, are potent inhibitors
of human colon adenocarcinoma cell growth, carcinogen-induced biochemical
changes, and preneoplastic lesions in the rat colon. The present study was
designed to investigate the chemopreventive action of dietary phenylethyl-3-methylcaffeate
(PEMC) on azoxymethane-induced colon carcinogenesis and to examine the modulating
effect of PEMC on phosphatidylinositol-specific phospholipase C (PI-PLC),
phospholipase A2, lipoxygenase (LOX), and cyclooxygenase activities in the
colonic mucosa and tumor tissues in male F344 rats. At 5 weeks of age, groups
of rats were fed the control (modified AIN-76A) diet, or a diet containing
750 ppm of PEMC. At 7 weeks of age, all animals except those in the vehicle
(normal saline)-treated groups were given 2 weekly s.c. injections of azoxymethane
at a dose rate of 15 mg/kg body weight/week. All groups were maintained on
their respective dietary regimen until the termination of the experiment 52
weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically.
Both colonic mucosa and tumors were analyzed for PI-PLC, phospholipase A2,
cyclooxygenase, and LOX activities. The results indicate that dietary administration
of PEMC significantly inhibited the incidence and multiplicity of invasive,
noninvasive, and total (invasive plus noninvasive) adenocarcinomas of the
colon (P < 0.05-0.004). Dietary PEMC also suppressed the colon tumor volume
by 43% compared to the control diet. Animals fed the PEMC diet showed significantly
decreased activities of colonic mucosal and tumor PI-PLC (about 50%), but
PEMC diet had no effect on phospholipase A2. The production of 5(S)-, 8(S)-,
12(S)-, and 15(S)-hydroxyeicosatetraenoic acids via the LOX pathway from arachidonic
acid was reduced in colonic mucosa and tumors (30-60%) of animals fed the
PEMC diet as compared to control diet. PEMC had no effect on the formation
of colonic mucosal cyclooxygenase metabolites but inhibited the formation
in colonic tumors by 15-30%. The precise mechanism by which PEMC inhibits
colon tumorigenesis remains to be elucidated. It is likely that the chemopreventive
action may be related, at least in part, to the modulation of PI-PLC-dependent
signal transduction and LOX-mediated arachidonic acid metabolism.
PMID: 7757981 [PubMed - indexed for MEDLINE]
| 70: Cancer Res. 1994 Apr 1;54(7):1865-70. |
Growth suppression and toxicity
induced by caffeic acid phenethyl ester (CAPE) in type 5 adenovirus-transformed
rat embryo cells correlate directly with transformation progression.
Su ZZ, Lin J, Grunberger D,
Fisher PB.
Department of Urology, Columbia University, College of Physicians and Surgeons,
New York, New York 10032.
The active component of the honeybee hive product propolis, caffeic acid phenethyl
ester (CAPE), induces a selective growth suppressive and toxic effect toward
cloned rat embryo fibroblast cells transformed by adenovirus type 5 (Ad5)
or the Ad5 E1A transforming gene versus untransformed cloned rat embryo fibroblast
cells (Z-z. Su et al., Mol. Carcinog., 4: 231-242, 1991). The present study
was conducted to determine whether CAPE-induced growth suppression/toxicity
was a direct result of expression of the Ad5 E1A and E1B transforming genes
or a consequence of the action of these genes resulting in the transformed
state. For this investigation we used somatic cell hybrids and 5-azacytidine-treated
Ad5-transformed rat embryo cells that display different stages of expression
of the transformed phenotype. This series of cell lines has permitted us to
determine whether expression of the transformed state and the stage of transformation
progression regulates CAPE sensitivity. Evidence is presented indicating that
sensitivity to CAPE is directly determined by the state of expression of the
transformed progression phenotype, as opposed to simply the expression of
the Ad5 E1A and E1B transforming genes. These results provide further evidence
that CAPE may represent a unique compound that can specifically target progressed
transformed cells for growth suppression and toxicity. An understanding of
the mechanism underlying this selective effect of CAPE could result in the
identification of important biochemical pathways mediating cellular transformation
and progression of the transformed state.
PMID: 7511055 [PubMed - indexed for MEDLINE]
| 71: Cancer Res. 1993 Sep 15;53(18):4182-8. |
Inhibitory effect of caffeic
acid esters on azoxymethane-induced biochemical changes and aberrant crypt
foci formation in rat colon.
Rao CV, Desai D, Simi B, Kulkarni N, Amin S, Reddy BS.
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla,
New York 10595.
Previous work from this laboratory established that caffeic acid esters, present
in the propolis of honey bee hives, are potent inhibitors of human colon tumor
cell growth, suggesting that these compounds may possess antitumor activity
against colon carcinogenesis. The present study was designed to investigate
(a) the inhibitory effects of methyl caffeate (MC) and phenylethyl caffeate
(PEC) on azoxymethane (AOM)-induced ornithine decarboxylase (ODC), tyrosine
protein kinase (TPK), and arachidonic acid metabolism in liver and colonic
mucosa of male F344 rats, (b) the effects of caffeic acid, MC, PEC, phenylethyl-3-methylcaffeate
(PEMC), and phenylethyl dimethylcaffeate (PEDMC) on in vitro arachidonic acid
metabolism in liver and colonic mucosa, and (c) the effects of PEC, PEMC,
and PEDMC on AOM-induced aberrant crypt foci (ACF) formation in the colon
of F344 rats. At 5 weeks of age, groups of animals were fed diets containing
600 ppm MC or PEC (biochemical study) or 500 ppm PEC, PEMC, or PEDMC (ACF
study). Two weeks later, all animals except the vehicle-treated groups were
given s.c. injections of AOM, once weekly for 2 weeks. The animals intended
for the biochemical study were sacrificed 5 days later and colonic mucosa
and liver were analyzed for ODC, TPK, lipoxygenase, and cyclooxygenase metabolites.
The animals intended for the ACF study were sacrificed 9 weeks later and analyzed
for ACF in the colon. The results indicate that the PEC diet significantly
inhibited AOM-induced ODC (P < 0.05) and TPK (P < 0.001) activities
in liver and colon. The PEC diet significantly (P < 0.001) suppressed the
AOM-induced lipoxygenase metabolites 8(S)- and 12(S)-hydroxyeicosatetraenoic
acid (HETE). The animals fed the MC diet exhibited a moderate inhibitory effect
on ODC and 5(S)-, 8(S)-, 12(S)-, and 15(S)-HETEs and a significant (P <
0.001) effect on colonic TPK activity. However, the MC and PEC diets showed
no significant inhibitory effects on cyclooxygenase metabolism. In an in vitro
study, caffeic acid and MC showed inhibitory effects on HETE formation only
at a 100 microM concentration, whereas PEC, PEMC, and PEDMC suppressed in
vitro HETE formation in a dose-dependent manner. AOM-induced colonic ACF were
significantly inhibited in the animals fed PEC (55%), PEMC (82%), or PEDMC
(81%). The results of the present study indicate that PEC, PEMC, and PEDMC,
present in honey, inhibit AOM-induced colonic preneoplastic lesions, ODC,
TPK, and lipoxygenase activity, which are relevant to colon carcinogenesis.
PMID: 8364913 [PubMed - indexed for MEDLINE]
| 72: Cancer Res. 1993 Mar 15;53(6):1255-61. |
Inhibition of tumor promoter-mediated
processes in mouse skin and bovine lens by caffeic acid phenethyl ester.
Frenkel K, Wei H, Bhimani R, Ye J, Zadunaisky JA,
Huang MT, Ferraro T, Conney AH, Grunberger D.
Department of Environmental Medicine, New York University Medical Center,
New York 10016-6451.
Caffeic acid phenethyl ester (CAPE) was isolated from propolis (a product
of honeybee hives) that has been used in folk medicine as a potent antiinflammatory
agent. CAPE is cytotoxic to tumor and virally transformed but not to normal
cells. Our main goal was to establish whether CAPE inhibits the tumor promoter
(12-O-tetradecanoylphorbol-13-acetate)-induced processes associated with carcinogenesis.
Topical treatment of SENCAR mice with very low doses (0.1-6.5 nmol/topical
treatment) of CAPE strongly inhibits the following 12-O-tetradecanoylphorbol-13-acetate-mediated
oxidative processes that are considered essential for tumor promotion: (a)
polymorphonuclear leukocyte infiltration into mouse skin and ears, as quantified
by myeloperoxidase activity; (b) hydrogen peroxide (H2O2) production; and
(c) formation of oxidized bases in epidermal DNA, as measured by 5-hydroxymethyluracil
and 8-hydroxylguanine. A 0.5-nmol dose of CAPE suppresses the oxidative burst
of human polymorphonuclear leukocytes by 50%. At higher doses (1-10 mumol),
CAPE inhibits edema and ornithine decarboxylase induction in CD-1 and SENCAR
mice. Interestingly, we discovered that 12-O-tetradecanoylphorbol-13-acetate-induced
H2O2 production in bovine lenses also is inhibited by CAPE. Cumulatively,
these findings point to CAPE as being a potent chemopreventive agent, which
may be useful in combating diseases with strong inflammatory and/or oxidative
stress components, i.e., various types of cancer and possibly cataract development.
PMID: 7680281 [PubMed - indexed for MEDLINE]
| 73: Chem Biol Interact. 1992 Nov 16;84(3):277-90. |
Effect of caffeic acid esters
on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth.
Rao CV, Desai D, Kaul B, Amin S, Reddy BS.
Division of Nutritional Carcinogenesis, American Health Foundation, Valhalla,
New York.
Propolis, a honey bee hive product, is thought to exhibit a broad spectrum
of activities including antibiotic, antiviral, anti-inflammatory and tumor
growth inhibition; some of the observed biological activities may be due to
caffeic acid (cinnamic acid) esters that are present in propolis. In the present
study we synthesized three caffeic acid esters, namely methyl caffeate (MC),
phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested
them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary
carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and
TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma,
HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine
kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium
strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB
and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80
microM PEDMC were determined. The results indicate that MC, PEC and PEDMC
were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity
was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80
microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma
cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly
inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK
activities were also inhibited in HT-29 cells treated with different concentrations
of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which
are present in Propolis possess chemopreventive properties when tested in
short-term assay systems.
PMID: 1423745 [PubMed - indexed for MEDLINE]
| 74: Cell Mol Biol. 1992 Aug;38(5):513-27. |
Erratum in:
· Cell Mol Biol 1992 Sep;38(6):615.
Growth inhibition and modulation
of antigenic phenotype in human melanoma and glioblastoma multiforme cells
by caffeic acid phenethyl ester (CAPE)
Guarini L, Su ZZ, Zucker S, Lin J, Grunberger D,
Fisher PB.
Division of Pediatric Hematology/Oncology, Columbia University, College of
Physicians and Surgeons, New York, New York 10032.
The active component of the honeybee hive product propolis, caffeic acid phenethyl
ester (CAPE), has been shown to display increased toxicity toward various
oncogene-transformed cell lines in comparison with their untransformed counterparts
(Su et al., 4: 231-242, 1991). This observation provides support for the concept
that it is the transformed phenotype which is specifically sensitive to CAPE.
In the present study, we have determined the effect of CAPE on the growth
and antigenic phenotype of a human melanoma cell line, HO-1, and a human glioblastoma
multiforme cell line, GBM-18. For comparison, we have also tested the effects
of mezerein (MEZ), mycophenolic acid (MPA) and retinoic acid (RA), which can
differentially modulate growth, differentiation and the antigenic phenotype
in these human tumor cell lines. Growth of both cell lines was suppressed
by CAPE in a dose-dependent fashion, with HO-1 cells being more sensitive
than GBM-18 cells. The antiproliferative effect of CAPE was enhanced in both
cell types if CAPE and MEZ were used in combination. Growth suppression was
associated with morphological changes in H0-1 cells, suggesting induction
of a more differentiated phenotype. CAPE also differentially modulated the
expression of several antigens on the surface of the two tumor cell lines.
These results suggest a potential role for CAPE as an antitumor agent, an
antigenic modulating agent and possibly a differentiation inducing agent.
PMID: 1281753 [PubMed - indexed for MEDLINE]
| 75: Mol Carcinog. 1991;4(3):231-42. |
Suppression of adenovirus type
5 E1A-mediated transformation and expression of the transformed phenotype
by caffeic acid phenethyl ester (CAPE).
Su ZZ, Grunberger D,
Fisher PB.
Department of Urology, Columbia University, College of Physicians and Surgeons,
New York 10032.
Viral transformation and DNA-transfection assays were employed to investigate
the differential toxic effect of caffeic acid phenethyl ester (CAPE), an extract
of the honeybee hive product propolis, on adenovirus type 5 (Ad5)-transformed
cloned rat embryo fibroblast (CREF) cells. CAPE inhibited, in a dose-dependent
manner, both de novo and carcinogen-enhanced transformation of CREF cells
by H5hr1, the cold-sensitive (cs) host-range mutant of Ad5. CAPE had a selective
inhibitory effect on Ad5-induced transformation when a wild-type (wt) Ad5
E1A gene or a cs Ad5 E1A gene (at 37 degrees C, but not at 32 degrees C) was
cotransfected into CREF cells with a dominant-acting bacterial hygromycin-resistance
gene. A requirement for the expression of Ad5 E1A-encoded mRNAs and transforming
proteins and sensitivity to CAPE was demonstrated using CREF cells stably
transformed by a cs Ad5 E1A gene and an Ad5 E1A gene under the transcriptional
control of a mouse mammary tumor virus promoter. To distinguish between the
effects of the two Ad5 E1A-encoded proteins of 289 amino acids (aa) and 243
aa, CREF cells were stably transformed with cDNAs encoding either the 13S
or the 12S E1A mRNA. CREF cells expressing the 13S E1A-encoded 289-aa protein
were more sensitive to the growth-suppressing effect of CAPE than cells producing
only the 12S E1A-encoded 243-aa protein. However, the growth-suppressing and
toxic effects of CAPE were greatest in cells expressing both E1A-encoded transforming
proteins. Analysis of the effect of CAPE on E1A and beta-actin gene expression
in wt and cs E1A and H5hr1-transformed CREF cells indicated that low levels
of CAPE, which were growth suppressive, did not selectively suppress E1A expression.
These results demonstrated that cellular changes induced in CREF cells by
the 13S E1A-encoded 289-aa protein of Ad5, when expressed alone or in combination
with the 12S E1A-encoded 243-aa protein, rendered transformed cells sensitive
to the growth-suppressing and toxic effects of CAPE.
PMID: 1712205 [PubMed - indexed for MEDLINE]
| 76: Z Naturforsch [C]. 1989 Nov-Dec;44(11-12):1063-5. |
Antitumoral property of ethanolic
extract of propolis in mice-bearing Ehrlich carcinoma, as compared to bleomycin.
Scheller S, Krol W, Swiacik J, Owczarek S, Gabrys J, Shani J.
Department of Microbiology, Silesian School of Medicine, Zabrze-Rokitnica,
Poland.
Antitumoral effect of ethanolic extract of propolis (EEP) was demonstrated
in mature mice-bearing Ehrlich carcinoma. Survival rate after EEP treatment
was compared to that of bleomycin, given alone or in combination every two
days for 36 days and followed up for 14 additional days. The survival rate
at 50 days was 55% after EEP and 40% after bleomycin, while all the mice-treated
with EEP + bleomycin combination demonstrated shorter survival than the controls.
It is concluded that while the in vivo activity of bleomycin is reduced in
the presence of cytochrome-C-reductase inhibitors (like some of the EEP components
are), the antitumoral property of EEP in the tumored animal model studied
is significant and lasting.
PMID: 2483616 [PubMed - indexed for MEDLINE]
| 77: Radiobiol Radiother (Berl). 1989;30(4):363-7. |
[The use of propolis preparations
in the treatment of radioepithelitis following telegammatherapy of the pharyngeal
region]
[Article in German]
Velikov P, Zanev M.
PMID: 2798801 [PubMed - indexed for MEDLINE]
| 78: Zhong Xi Yi Jie He Za Zhi. 1985 Aug;5(8):485-6, 452-3. |
[Treatment of oral leukoplakia
with propolis: report of 45 cases]
[Article in Chinese]
Pang JF, Chen SS.
PMID: 2932253 [PubMed - indexed for MEDLINE]
| 79: Biochem Pharmacol. 1983 Apr 1;32(7):1141-8. |
Flavonoids, a class of natural
products of high pharmacological potency.
Havsteen B.
A review has been presented of the biochemistry and pharmacology of a class
of natural products, the flavonoids. These substances which are widely distributed
in the plant kingdom and present in considerable quantities in common food
products, spices and beverages have in a concentrated form (Propolis) been
used since ancient times by physicians and laymen to treat a great variety
of human diseases but they have yet to pass the tests of modern, controlled,
clinical experimentation. An attempt has been made to present the fundamental
evidence from the basic biological sciences which is required to stimulate
the interest of the clinicians in this new field. The few existing reports
on the careful pharmacodynamic, pharmacokinetic and clinical studies which
have been made have been summarized to provide a basis for a full-scale investigation
of the therapeutic potential of flavonoids.
Publication Types:
· Review
PMID: 6342623 [PubMed - indexed for MEDLINE]