HER2 Support Group Forums - View Single Post - Green Tea/epigallocatechin-3-gallate (EGCG)

Rich66 · 03-06-2010, 09:32 PM

Telomerase related to cancer stem cell issues:

Int J Oncol. 2004 Mar;24(3):703-10.
EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis.

Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar SK.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied ( approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%). In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT. Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer.

PMID: 14767556 [PubMed - indexed for MEDLINE]

Cancer Lett. 2006 May 8;236(1):80-8. Epub 2005 Jun 21.
The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase reverse transcriptase (hTERT) in carcinoma cells.

Lin SC, Li WC, Shih JW, Hong KF, Pan YR, Lin JJ.
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Li-Nong St, Sec., 2, No155, Peitou, Taipei 112, Taiwan, ROC. sclin@ym.edu.tw
Tea polyphenols have inhibitive effects for carcinogenesis. A reporter system controlled by hTERT promoter was constructed to evaluate the effects of tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) on the repression of hTERT transcription. The hTERT promoter activity was selectively repressed by 20-40 microM EGCG and EGC in a dose- and time-dependent manner. Real-time RT-PCR confirmed that the endogenous hTERT mRNA level was decreased in H1299, OECM-1 and SAS cells treated with EGCG or EGC. Our results identified the repression activities of EGCG and EGC toward telomerase expression that might be linked to inhibition of carcinoma cell growth. This cell-based reporter system is useful for screening drugs targeting hTERT repression.

PMID: 15975707 [PubMed - indexed for MEDLINE]

Mol Biol Rep. 2009 May;36(5):1181-6. Epub 2008 Jun 26.
The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin.

Shervington A, Pawar V, Menon S, Thakkar D, Patel R.
Brain Tumour North West, Faculty of Science, University of Central Lancashire, Preston, UK. aashervington@uclan.ac.uk
Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate (EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h (P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly (P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour cell sensitivity to therapy.

PMID: 18581255 [PubMed - indexed for MEDLINE]

Cancer Detect Prev. 2007;31(6):499-504.
(-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells.

Farabegoli F, Barbi C, Lambertini E, Piva R.
Department of Experimental Pathology, University of Bologna, V.S. Giacomo 14, 40126 Bologna, Italy. fulvia.farabegoli@unibo.it
BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin present in green tea, demonstrated to have chemopreventive action and to kill cancer cells selectively. As a previous study found that catechins could compete with 17-beta-estradiol for binding to estrogen receptor alpha (ERalpha), we asked whether EGCG could regulate ERalpha action. METHODS: We used MCF-7, a breast carcinoma cell line having a high level of ERalpha expression. The cells were treated with various EGCG concentrations and cell viability was evaluated by MTT assay. ERalpha and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ERalpha, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10(-7)M ICI 182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERalpha by flow cytometry (FCM). RESULTS: Both ERalpha and pS2 mRNA were expressed in samples treated with low EGCG concentration (30 microg/ml). At this concentration, no cell change was detectable. In contrast, pS2 expression was lost in samples treated with 100 microg/ml EGCG for 24h, indicating ERalpha alteration. EGCG cytotoxicity was lower when ERalpha was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 182,780). CONCLUSIONS: Functionally active ERalpha may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher EGCG concentrations also killed cells resistant to tamoxifen or treated by 10(-7)M ICI 182,780, EGCG ought to be better investigated in breast carcinoma cells treated with drugs targeted to steroid receptors, as a potential complement of therapy.

PMID: 18061364 [PubMed - indexed for MEDLINE]

Carcinogenesis. 2006 Dec;27(12):2424-33. Epub 2006 Jun 19.
The combination of green tea and tamoxifen is effective against breast cancer.

Sartippour MR, Pietras R, Marquez-Garban DC, Chen HW, Heber D, Henning SM, Sartippour G, Zhang L, Lu M, Weinberg O, Rao JY, Brooks MN.
Department of Surgery, Center for Human Nutrition, University of California, Los Angeles, CA 90095-1782, USA.
Epidemiologic data have suggested that green tea may prevent breast cancer. Studies in our laboratory have provided evidence that green tea extract inhibits breast cancer growth by a direct anti-proliferative effect on the tumor cells, as well as by indirect suppressive effects on the tumor-associated endothelial cells. In this study, we asked whether concurrent administration of green tea may add to the anti-tumor effects of standard breast cancer therapy. We observed that green tea increased the inhibitory effect of tamoxifen on the proliferation of the ER (estrogen receptor)-positive MCF-7, ZR75, T47D human breast cancer cells in vitro. This combination regimen was also more potent than either agent alone at increasing cell apoptosis. In animal experiments, mice treated with both green tea and tamoxifen had the smallest MCF-7 xenograft tumor size, and the highest levels of apoptosis in tumor tissue, as compared with either agent administered alone. Moreover, the suppression of angiogenesis in vivo correlated with larger areas of necrosis and lower tumor blood vessel density in treated xenografts. Green tea decreased levels of ER-alpha in tumors both in vitro and in vivo. We also observed that green tea blocked ER-dependent transcription, as well as estradiol-induced phosphorylation and nuclear localization of mitogen-activated protein kinase. To our knowledge, this study is the first to show the interaction of green tea with the ER pathway, as well as provide mechanistic evidence that the combination of green tea and tamoxifen is more potent than either agent alone in suppressing breast cancer growth. These results may lead to future improvements in breast cancer treatment and prevention.

PMID: 16785249 [PubMed - indexed for MEDLINE]

Anticancer Drugs. 2004 Oct;15(9):889-97.
Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells.

Chisholm K, Bray BJ, Rosengren RJ.
Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
High concentrations of specific catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC) and epicatechin gallate (ECG)] inhibit the proliferation of many different cancer cell lines. The aim of this work was to determine if low concentrations of catechins with and without 4-hydroxytamoxifen (4-OHT) co-treatment would cause significant cytotoxicity in estrogen receptor-positive (ERalpha+) and -negative (ERalpha-) human breast cancer cells. Therefore, MCF-7, T47D, MDA-MB-231 and HS578T cells were incubated with EGCG, EGC or ECG (5-25 microM) individually and in combination with 4-OHT for 7 days. Cell number was determined by the sulforhodamine B cell proliferation assay. As single agents, none of the catechins were cytotoxic to T47D cells, while only EGCG (20 microM) elicited cytotoxicity in MCF-7 cells. Additionally, no benefit was gained by combination treatment with 4-OHT. ERalpha- human breast cancer cells were more susceptible as all three catechins were significantly cytotoxic to HS578T cells at concentrations of 10 microM. In this cell line, combination with 4-OHT did not increase cytotoxicity. However, the most striking results were produced in MDA-MB-231 cells. In this cell line, EGCG (25 microM) produced a greater cytotoxic effect than 4-OHT (1 microM) and the combination of the two resulted in synergistic cytotoxicity. In conclusion, low concentrations of catechins are cytotoxic to ERalpha- human breast cancer cells, and the combination of EGCG and 4-OHT elicits synergistic cytotoxicity in MDA-MB-231 cells.

PMID: 15457130 [PubMed - indexed for MEDLINE]

J Biochem Mol Biol. 2005 Sep 30;38(5):563-70.
Hepatoprotective effect of green tea (Camellia sinensis) extract against tamoxifen-induced liver injury in rats.

El-Beshbishy HA.
Biochemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt. Hesham_Elbeshbishy@hotmail.com
Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced liver injury. A model of liver injury in female rats was done by intraperitoneal injection of TAM in a dose of 45mg Kg(-1) day(-1), i.p. for 7 successive days. GTE in the concentration of 1.5 %, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in liver homogenate of tamoxifenintoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of 1.5 % GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases levels. The data obtained from this study speculated that 1.5 % GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced liver injury in rats.

PMID: 16202236 [PubMed - indexed for MEDLINE]

Cancer Detect Prev. 2000;24(1):91-9.
A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea--a review.

Fujiki H, Suganuma M, Okabe S, Sueoka E, Suga K, Imai K, Nakachi K.
Saitama Cancer Center Research Institute, Kitaadachi-gun, Japan.
The study of tumor promotion in rodent carcinogenesis using chemical tumor promoters has revealed various tumor promotion pathways, such as the 12-O-tetradecanoylphorbol-13-acetate (TPA) pathway mediated through activation of protein kinase C, and the okadaic acid pathway mediated through inhibition of protein phosphatases 1 and 2A (PP-1 and PP-2A). We previously demonstrated that application of TPA and okadaic acid induced tumor necrosis factor-alpha (TNF-alpha) gene expression in mouse skin, but that tautomycin, which is an inhibitor of PP-1 and PP-2A and not a tumor promoter on mouse skin, did not. Moreover, we found that TNF-alpha stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene 1,000 times stronger than did TPA (Cancer Res. 53, 1982-1985, 1993). This evidence demonstrates a link between the okadaic acid pathway and the endogenous tumor promotion pathway of TNF-alpha. Recently we presented the first evidence that tumor promotion in TNF-alpha(-/-) mice was significantly depressed compared with TNF-alpha(+/+) mice. Thus, in human carcinogenesis, we think that TNF-alpha and other inflammatory cytokines in preneoplastic lesion stimulate tumor promotion and progression of initiated cells as well as premalignant cells. The first part of this paper reports on this TNF-alpha tumor promotion pathway. In the second part, we report a promising screening method for cancer preventive agents, based on evidence that pretreatment with agents such as tamoxifen, sulindac, 1alpha, 25-(OH)2 vitamin D3, quercetin, caffeic acid phenethyl ester, and (-)-epigallocatechin gallate (EGCG) commonly inhibited TNF-alpha release from BALB/3T3 cells induced by okadaic acid. EGCG, the main constituent of Japanese green tea, and green tea itself are acknowledged cancer preventives in Japan, and this paper presents evidence of their effectiveness in both a high-risk group and the general population.

PMID: 10757128 [PubMed - indexed for MEDLINE]

J Surg Res. 2007 Jul;141(1):115-9.
Dietary influence on pancreatic cancer growth by catechin and inositol hexaphosphate.

McMillan B, Riggs DR, Jackson BJ, Cunningham C, McFadden DW.
Department Of Surgery, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia, USA.
Abstract

INTRODUCTION: Pancreatic cancer is an extremely virulent form of cancer with few effective treatments. We hypothesized that, alone and in combination, IP6 and catechin would be effective against pancreatic cancer. MATERIALS AND METHODS: Pancreatic (PANC-1 and MIAPACA) cancer cell lines were cultured and treated with IP6 (0.8 mM/well), catechin (100 microM/well), and the combination of the two. Cell viability was measured by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) at 24, 48, and 72 h. Vascular endothelial growth factor (VEGF) was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC). RESULTS: Catechin and inositol hexaphosphate (IP6), two naturally occurring molecules found in green tea and high-fiber foods, respectively, are compounds that have been shown to demonstrate anti-proliferative effects when administered as single therapeutic agents against a number of cancers.The combination of catechin and IP6 significantly inhibited proliferation in the PANC-1 cell line at 24, 48, and 72 h compared to single agents (P < 0.001). Growth of the MIAPACA cell line was inhibited (P < 0.01) by each agent alone, but additive inhibitory effects were not seen. An increase in early apoptosis was attributed to catechin therapy in both cell lines (P < 0.01). The combination of these agents also increased early apoptotic activity when compared to the control (P < 0.001). IP6 reduced VEGF in both cell lines (P < 0.01). In combination, catechin and IP6 amplified VEGF reduction compared to each agent in MIAPACA and control (P < 0.002). CONCLUSIONS: These results, combined with the prevalence of these compounds in safe, naturally occurring foods, make catechin and IP6 attractive therapies for treatment, and possibly in preventative trials, of pancreatic cancer.

PMID: 17574044 [PubMed - indexed for MEDLINE]

Pharm Res. 2010 Jun;27(6):1103-14. Epub 2010 Mar 16.
Anti-melanoma effects of vorinostat in combination with polyphenolic antioxidant (-)-epigallocatechin-3-gallate (EGCG).

Nihal M, Roelke CT, Wood GS.
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Room B25, Madison, Wisconsin 53706, USA.
Abstract

PURPOSE: Melanoma is an aggressive neoplasm with a propensity for metastases and resistance to therapy. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, resulted in a significant decrease in the viability and growth of melanoma and induction of apoptosis via modulation of the cki-cdk-cyclin network and Bcl2 family proteins. Epigenetic regulation of gene transcription by histone deacetylase (HDAC) inhibitors is gaining momentum as a novel cancer therapy. SAHA-suberoylanilidine hydroxamic acid Zolinza (vorinostat) is the first HDAC inhibitor approved by the U.S. FDA. In this study, we determined if vorinostat alone or in combination with EGCG imparts anti-proliferative effects against human melanoma cells. METHODS: Employing human melanoma cell lines A-375, Hs-294T and G-361, we determined the effect of vorinostat and/or EGCG on 1) growth/viability and colony formation, 2) apoptosis, and 3) the critical molecules involved in cell cycle and apoptosis regulation. RESULTS: Our data demonstrated that the anti-proliferative effects of vorinostat were greater than or similar to those of EGCG among the cell lines tested. Furthermore, relative to monotherapy, the combination treatment resulted in significantly greater inhibition of cell proliferation, increased apoptosis, activation of p21, p27 and caspases (3, 7 and 9) and Bax as well as down-regulation of cdk2, cdk4, cyclin A, NF-kappaB protein p65/RelA and Bcl2 protein and transcript. CONCLUSIONS: Our preclinical findings suggest that combination therapy with EGCG and vorinostat may be beneficial for the management of human melanoma.

PMID: 20232120 [PubMed - in process]

Cell Cycle. 2009 Jul 1;8(13):2057-63. Epub 2009 Jul 27.
(-)-Epigallocatechin-3-gallate (EGCG) sensitizes melanoma cells to interferon induced growth inhibition in a mouse model of human melanoma.

Nihal M, Ahsan H, Siddiqui IA, Mukhtar H, Ahmad N, Wood GS.
Department of Dermatology, University of Wisconsin Medical School and William S. Middleton VA Medical Center, Madison, WI 53706, USA.
Comment in:

Cell Cycle. 2009 Jul 1;8(13):1979-80.

Abstract

Melanoma incidence has increased over the last few decades and metastatic melanoma is one of the hardest malignancies to treat. Thus, novel approaches are needed for an effective management of melanoma. Interferon-alpha2b (IFN), an immunomodulatory cytokine commonly used in melanoma treatment, has shown marginal efficacy and often results in discontinuation of therapy due to toxicity. We earlier demonstrated that epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, caused cell cycle arrest and apoptosis of human melanoma cells via modulation in cki-cyclin-cdk machinery and Bcl-2 family proteins. This study was undertaken to determine if EGCG could enhance the anti-proliferative effects of IFN. In this study, we demonstrated that EGCG and/or IFN treatments to melanoma cells resulted in a marked (1) decrease in cell proliferation and colony formation ability, and (2) induction of apoptosis. Interestingly, the combination was found to be more effective than either of the agents alone. Further, the anti-proliferative effects of EGCG and/or IFN were accompanied with an increase in Fas protein levels and a decrease in nuclear factor NFkappaB/p65 in the nucleus as well as NFkappaB promoter activity. EGCG and/or IFN also resulted in an increase in Fas-L mediated apoptosis. Further, EGCG and/or IFN treatments resulted in a decrease in melanoma tumor growth and protein levels of proliferation marker PCNA, in athymic nude mice implanted with melanoma tumors. The combination of the two modalities demonstrated a better response than either of them alone. Our data suggest that EGCG could impart therapeutic advantage if used in conjunction with IFN.

PMID: 19502799 [PubMed - indexed for MEDLINE]

Photomed Laser Surg. 2010 May 3. [Epub ahead of print]
Extraordinary Anticancer Effect of Green Tea and Red Light.

Sommer AP, Zhu D, Scharnweber T.
1 Institute of Micro and Nanomaterials, University of Ulm , Ulm, Germany .

Abstract

Abstract Objective: Increasing observational evidence suggests that epigallocatechin gallate-the major polyphenolic component of green tea-is instrumental in suppressing the growth of cancer cells. Therefore, methods that promise to enhance the suppressive potential of green tea have the highest clinical relevance. Background Data: Human cervical cancer cells, HeLa, the first continuous cancer cell line, represent a mainstay model in cancer research. Green tea inhibited their growth, whereas their exposure to moderate levels of laser light resulted in an opposite effect. Both effects are individually documented in the literature. Methods: HeLa cells were supplemented with green tea, irradiated with moderately intense laser light (670 nm) for 1 min, and incubated for 52 h. Results: We found an extraordinary inhibition of HeLa cells by a combination of green tea and red light. We achieved an inhibition of 1,460%, compared with non-irradiated samples. Conclusion: Our result receives clinical relevance from a recent study in which epigallocatechin gallate suppressed the growth of melanoma in vivo.

PMID: 20438353 [PubMed - as supplied by publisher]

03-06-2010, 09:32 PM	#3
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Green Tea/epigallocatechin-3-gallate (EGCG) Telomerase related to cancer stem cell issues: Int J Oncol. 2004 Mar;24(3):703-10. EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis. Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar SK. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Telomerase is elevated in >90% of breast carcinomas and therefore has received much attention as a target for breast cancer therapy and cancer diagnostic research. Dietary components that are capable of inhibiting the growth of cancer cells without affecting the growth of normal cells are receiving considerable attention in developing novel cancer-preventive approaches. Studies have shown that (-)-epigallocatechin-3-gallate (EGCG) from green tea imparts a growth inhibitory effect on cancer cells. Here, we show that treatment of EGCG dose-dependently inhibited (20-100%) the reproductive or colony forming potential, and also decreased cell viability at different time points studied ( approximately 80% inhibition) in human breast carcinoma MCF-7 cells but had no adverse effect on the growth of normal mammary cells. Treatment of EGCG for 48 and 72 h markedly increased the percentage of apoptotic cells (32-51%) in MCF-7 cells compared to that of non-EGCG treated cells (8-14%). In order to identify the possible mechanism of decreased cell viability and induction of apoptosis in breast carcinoma cells by EGCG, we found that treatment of MCF-7 cells with EGCG dose-dependently inhibited telomerase activity (40-55%), and also inhibited the mRNA expression (40-55%) of hTERT, a catalytic subunit of telomerase. Additional studies demonstrated that EGCG also inhibited the protein expression of hTERT, which indicated that inhibition of telomerase was associated with down-regulation of hTERT. Together, our results indicate that EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to the suppression of cell viability and induction of apoptosis, thus providing the molecular basis for the development of EGCG as a novel chemopreventive and pharmacologically safe agent against breast cancer. PMID: 14767556 [PubMed - indexed for MEDLINE] Cancer Lett. 2006 May 8;236(1):80-8. Epub 2005 Jun 21. The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase reverse transcriptase (hTERT) in carcinoma cells. Lin SC, Li WC, Shih JW, Hong KF, Pan YR, Lin JJ. Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Li-Nong St, Sec., 2, No155, Peitou, Taipei 112, Taiwan, ROC. sclin@ym.edu.tw Tea polyphenols have inhibitive effects for carcinogenesis. A reporter system controlled by hTERT promoter was constructed to evaluate the effects of tea polyphenols, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epigallocatechin (EGC) on the repression of hTERT transcription. The hTERT promoter activity was selectively repressed by 20-40 microM EGCG and EGC in a dose- and time-dependent manner. Real-time RT-PCR confirmed that the endogenous hTERT mRNA level was decreased in H1299, OECM-1 and SAS cells treated with EGCG or EGC. Our results identified the repression activities of EGCG and EGC toward telomerase expression that might be linked to inhibition of carcinoma cell growth. This cell-based reporter system is useful for screening drugs targeting hTERT repression. PMID: 15975707 [PubMed - indexed for MEDLINE] Mol Biol Rep. 2009 May;36(5):1181-6. Epub 2008 Jun 26. The sensitization of glioma cells to cisplatin and tamoxifen by the use of catechin. Shervington A, Pawar V, Menon S, Thakkar D, Patel R. Brain Tumour North West, Faculty of Science, University of Central Lancashire, Preston, UK. aashervington@uclan.ac.uk Telomerase expression strongly correlates with the grade of malignancy in glioma with inhibition illustrating a definite increase in chemosensitivity. This study was designed to investigate the effects of a green tea derivative, epigallocatechin-3-gallate (EGCG); together with either cisplatin or tamoxifen in glioma, and to investigate whether these effects are mediated through telomerase suppression. EGCG showed a significant cytotoxic effect on 1321N1 cells after 24 h and on U87-MG cells after 72 h (P < 0.001) without significantly affecting the normal astrocytes. Treatment with EGCG inhibited telomerase expression significantly (P < 0.01) and enhanced the effect of cisplatin and tamoxifen in both 1321N1 (P < 0.01) and U87-MG (P < 0.001) cells. EGCG, as a natural product has enormous potential to be an anti-cancer agent capable of enhancing tumour cell sensitivity to therapy. PMID: 18581255 [PubMed - indexed for MEDLINE] Cancer Detect Prev. 2007;31(6):499-504. (-)-Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells. Farabegoli F, Barbi C, Lambertini E, Piva R. Department of Experimental Pathology, University of Bologna, V.S. Giacomo 14, 40126 Bologna, Italy. fulvia.farabegoli@unibo.it BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is the most active catechin present in green tea, demonstrated to have chemopreventive action and to kill cancer cells selectively. As a previous study found that catechins could compete with 17-beta-estradiol for binding to estrogen receptor alpha (ERalpha), we asked whether EGCG could regulate ERalpha action. METHODS: We used MCF-7, a breast carcinoma cell line having a high level of ERalpha expression. The cells were treated with various EGCG concentrations and cell viability was evaluated by MTT assay. ERalpha and pS2 expression were analyzed by RT-PCR after RNA extraction. To better define EGCG action in relation to ERalpha, we studied EGCG cytotoxicity on MCF-7 resistant to tamoxifen (MCF-7tam), MCF-7 treated with 10(-7)M ICI 182,780 for 8 days and on MDA-MB-231, a cell line that lacked ERalpha by flow cytometry (FCM). RESULTS: Both ERalpha and pS2 mRNA were expressed in samples treated with low EGCG concentration (30 microg/ml). At this concentration, no cell change was detectable. In contrast, pS2 expression was lost in samples treated with 100 microg/ml EGCG for 24h, indicating ERalpha alteration. EGCG cytotoxicity was lower when ERalpha was not present (MDA-MB-231) or inactivated (by tamoxifen or ICI 182,780). CONCLUSIONS: Functionally active ERalpha may have a role in EGCG cytotoxicity, increasing the sensitivity to the drug. As higher EGCG concentrations also killed cells resistant to tamoxifen or treated by 10(-7)M ICI 182,780, EGCG ought to be better investigated in breast carcinoma cells treated with drugs targeted to steroid receptors, as a potential complement of therapy. PMID: 18061364 [PubMed - indexed for MEDLINE] Carcinogenesis. 2006 Dec;27(12):2424-33. Epub 2006 Jun 19. The combination of green tea and tamoxifen is effective against breast cancer. Sartippour MR, Pietras R, Marquez-Garban DC, Chen HW, Heber D, Henning SM, Sartippour G, Zhang L, Lu M, Weinberg O, Rao JY, Brooks MN. Department of Surgery, Center for Human Nutrition, University of California, Los Angeles, CA 90095-1782, USA. Epidemiologic data have suggested that green tea may prevent breast cancer. Studies in our laboratory have provided evidence that green tea extract inhibits breast cancer growth by a direct anti-proliferative effect on the tumor cells, as well as by indirect suppressive effects on the tumor-associated endothelial cells. In this study, we asked whether concurrent administration of green tea may add to the anti-tumor effects of standard breast cancer therapy. We observed that green tea increased the inhibitory effect of tamoxifen on the proliferation of the ER (estrogen receptor)-positive MCF-7, ZR75, T47D human breast cancer cells in vitro. This combination regimen was also more potent than either agent alone at increasing cell apoptosis. In animal experiments, mice treated with both green tea and tamoxifen had the smallest MCF-7 xenograft tumor size, and the highest levels of apoptosis in tumor tissue, as compared with either agent administered alone. Moreover, the suppression of angiogenesis in vivo correlated with larger areas of necrosis and lower tumor blood vessel density in treated xenografts. Green tea decreased levels of ER-alpha in tumors both in vitro and in vivo. We also observed that green tea blocked ER-dependent transcription, as well as estradiol-induced phosphorylation and nuclear localization of mitogen-activated protein kinase. To our knowledge, this study is the first to show the interaction of green tea with the ER pathway, as well as provide mechanistic evidence that the combination of green tea and tamoxifen is more potent than either agent alone in suppressing breast cancer growth. These results may lead to future improvements in breast cancer treatment and prevention. PMID: 16785249 [PubMed - indexed for MEDLINE] Anticancer Drugs. 2004 Oct;15(9):889-97. Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancer cells. Chisholm K, Bray BJ, Rosengren RJ. Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand. High concentrations of specific catechins [epigallocatechin gallate (EGCG), epigallocatechin (EGC) and epicatechin gallate (ECG)] inhibit the proliferation of many different cancer cell lines. The aim of this work was to determine if low concentrations of catechins with and without 4-hydroxytamoxifen (4-OHT) co-treatment would cause significant cytotoxicity in estrogen receptor-positive (ERalpha+) and -negative (ERalpha-) human breast cancer cells. Therefore, MCF-7, T47D, MDA-MB-231 and HS578T cells were incubated with EGCG, EGC or ECG (5-25 microM) individually and in combination with 4-OHT for 7 days. Cell number was determined by the sulforhodamine B cell proliferation assay. As single agents, none of the catechins were cytotoxic to T47D cells, while only EGCG (20 microM) elicited cytotoxicity in MCF-7 cells. Additionally, no benefit was gained by combination treatment with 4-OHT. ERalpha- human breast cancer cells were more susceptible as all three catechins were significantly cytotoxic to HS578T cells at concentrations of 10 microM. In this cell line, combination with 4-OHT did not increase cytotoxicity. However, the most striking results were produced in MDA-MB-231 cells. In this cell line, EGCG (25 microM) produced a greater cytotoxic effect than 4-OHT (1 microM) and the combination of the two resulted in synergistic cytotoxicity. In conclusion, low concentrations of catechins are cytotoxic to ERalpha- human breast cancer cells, and the combination of EGCG and 4-OHT elicits synergistic cytotoxicity in MDA-MB-231 cells. PMID: 15457130 [PubMed - indexed for MEDLINE] J Biochem Mol Biol. 2005 Sep 30;38(5):563-70. Hepatoprotective effect of green tea (Camellia sinensis) extract against tamoxifen-induced liver injury in rats. El-Beshbishy HA. Biochemistry Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt. Hesham_Elbeshbishy@hotmail.com Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced liver injury. A model of liver injury in female rats was done by intraperitoneal injection of TAM in a dose of 45mg Kg(-1) day(-1), i.p. for 7 successive days. GTE in the concentration of 1.5 %, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in liver homogenate of tamoxifenintoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of 1.5 % GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases levels. The data obtained from this study speculated that 1.5 % GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced liver injury in rats. PMID: 16202236 [PubMed - indexed for MEDLINE] Cancer Detect Prev. 2000;24(1):91-9. A new concept of tumor promotion by tumor necrosis factor-alpha, and cancer preventive agents (-)-epigallocatechin gallate and green tea--a review. Fujiki H, Suganuma M, Okabe S, Sueoka E, Suga K, Imai K, Nakachi K. Saitama Cancer Center Research Institute, Kitaadachi-gun, Japan. The study of tumor promotion in rodent carcinogenesis using chemical tumor promoters has revealed various tumor promotion pathways, such as the 12-O-tetradecanoylphorbol-13-acetate (TPA) pathway mediated through activation of protein kinase C, and the okadaic acid pathway mediated through inhibition of protein phosphatases 1 and 2A (PP-1 and PP-2A). We previously demonstrated that application of TPA and okadaic acid induced tumor necrosis factor-alpha (TNF-alpha) gene expression in mouse skin, but that tautomycin, which is an inhibitor of PP-1 and PP-2A and not a tumor promoter on mouse skin, did not. Moreover, we found that TNF-alpha stimulated transformation of BALB/3T3 cells initiated with 3-methylcholanthrene 1,000 times stronger than did TPA (Cancer Res. 53, 1982-1985, 1993). This evidence demonstrates a link between the okadaic acid pathway and the endogenous tumor promotion pathway of TNF-alpha. Recently we presented the first evidence that tumor promotion in TNF-alpha(-/-) mice was significantly depressed compared with TNF-alpha(+/+) mice. Thus, in human carcinogenesis, we think that TNF-alpha and other inflammatory cytokines in preneoplastic lesion stimulate tumor promotion and progression of initiated cells as well as premalignant cells. The first part of this paper reports on this TNF-alpha tumor promotion pathway. In the second part, we report a promising screening method for cancer preventive agents, based on evidence that pretreatment with agents such as tamoxifen, sulindac, 1alpha, 25-(OH)2 vitamin D3, quercetin, caffeic acid phenethyl ester, and (-)-epigallocatechin gallate (EGCG) commonly inhibited TNF-alpha release from BALB/3T3 cells induced by okadaic acid. EGCG, the main constituent of Japanese green tea, and green tea itself are acknowledged cancer preventives in Japan, and this paper presents evidence of their effectiveness in both a high-risk group and the general population. PMID: 10757128 [PubMed - indexed for MEDLINE] J Surg Res. 2007 Jul;141(1):115-9. Dietary influence on pancreatic cancer growth by catechin and inositol hexaphosphate. McMillan B, Riggs DR, Jackson BJ, Cunningham C, McFadden DW. Department Of Surgery, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia, USA. Abstract INTRODUCTION: Pancreatic cancer is an extremely virulent form of cancer with few effective treatments. We hypothesized that, alone and in combination, IP6 and catechin would be effective against pancreatic cancer. MATERIALS AND METHODS: Pancreatic (PANC-1 and MIAPACA) cancer cell lines were cultured and treated with IP6 (0.8 mM/well), catechin (100 microM/well), and the combination of the two. Cell viability was measured by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) at 24, 48, and 72 h. Vascular endothelial growth factor (VEGF) was measured in the cell supernatants by ELISA. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC). RESULTS: Catechin and inositol hexaphosphate (IP6), two naturally occurring molecules found in green tea and high-fiber foods, respectively, are compounds that have been shown to demonstrate anti-proliferative effects when administered as single therapeutic agents against a number of cancers.The combination of catechin and IP6 significantly inhibited proliferation in the PANC-1 cell line at 24, 48, and 72 h compared to single agents (P < 0.001). Growth of the MIAPACA cell line was inhibited (P < 0.01) by each agent alone, but additive inhibitory effects were not seen. An increase in early apoptosis was attributed to catechin therapy in both cell lines (P < 0.01). The combination of these agents also increased early apoptotic activity when compared to the control (P < 0.001). IP6 reduced VEGF in both cell lines (P < 0.01). In combination, catechin and IP6 amplified VEGF reduction compared to each agent in MIAPACA and control (P < 0.002). CONCLUSIONS: These results, combined with the prevalence of these compounds in safe, naturally occurring foods, make catechin and IP6 attractive therapies for treatment, and possibly in preventative trials, of pancreatic cancer. PMID: 17574044 [PubMed - indexed for MEDLINE] Pharm Res. 2010 Jun;27(6):1103-14. Epub 2010 Mar 16. Anti-melanoma effects of vorinostat in combination with polyphenolic antioxidant (-)-epigallocatechin-3-gallate (EGCG). Nihal M, Roelke CT, Wood GS. Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, Room B25, Madison, Wisconsin 53706, USA. Abstract PURPOSE: Melanoma is an aggressive neoplasm with a propensity for metastases and resistance to therapy. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, resulted in a significant decrease in the viability and growth of melanoma and induction of apoptosis via modulation of the cki-cdk-cyclin network and Bcl2 family proteins. Epigenetic regulation of gene transcription by histone deacetylase (HDAC) inhibitors is gaining momentum as a novel cancer therapy. SAHA-suberoylanilidine hydroxamic acid Zolinza (vorinostat) is the first HDAC inhibitor approved by the U.S. FDA. In this study, we determined if vorinostat alone or in combination with EGCG imparts anti-proliferative effects against human melanoma cells. METHODS: Employing human melanoma cell lines A-375, Hs-294T and G-361, we determined the effect of vorinostat and/or EGCG on 1) growth/viability and colony formation, 2) apoptosis, and 3) the critical molecules involved in cell cycle and apoptosis regulation. RESULTS: Our data demonstrated that the anti-proliferative effects of vorinostat were greater than or similar to those of EGCG among the cell lines tested. Furthermore, relative to monotherapy, the combination treatment resulted in significantly greater inhibition of cell proliferation, increased apoptosis, activation of p21, p27 and caspases (3, 7 and 9) and Bax as well as down-regulation of cdk2, cdk4, cyclin A, NF-kappaB protein p65/RelA and Bcl2 protein and transcript. CONCLUSIONS: Our preclinical findings suggest that combination therapy with EGCG and vorinostat may be beneficial for the management of human melanoma. PMID: 20232120 [PubMed - in process] Cell Cycle. 2009 Jul 1;8(13):2057-63. Epub 2009 Jul 27. (-)-Epigallocatechin-3-gallate (EGCG) sensitizes melanoma cells to interferon induced growth inhibition in a mouse model of human melanoma. Nihal M, Ahsan H, Siddiqui IA, Mukhtar H, Ahmad N, Wood GS. Department of Dermatology, University of Wisconsin Medical School and William S. Middleton VA Medical Center, Madison, WI 53706, USA. Comment in: Cell Cycle. 2009 Jul 1;8(13):1979-80. Abstract Melanoma incidence has increased over the last few decades and metastatic melanoma is one of the hardest malignancies to treat. Thus, novel approaches are needed for an effective management of melanoma. Interferon-alpha2b (IFN), an immunomodulatory cytokine commonly used in melanoma treatment, has shown marginal efficacy and often results in discontinuation of therapy due to toxicity. We earlier demonstrated that epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent of green tea, caused cell cycle arrest and apoptosis of human melanoma cells via modulation in cki-cyclin-cdk machinery and Bcl-2 family proteins. This study was undertaken to determine if EGCG could enhance the anti-proliferative effects of IFN. In this study, we demonstrated that EGCG and/or IFN treatments to melanoma cells resulted in a marked (1) decrease in cell proliferation and colony formation ability, and (2) induction of apoptosis. Interestingly, the combination was found to be more effective than either of the agents alone. Further, the anti-proliferative effects of EGCG and/or IFN were accompanied with an increase in Fas protein levels and a decrease in nuclear factor NFkappaB/p65 in the nucleus as well as NFkappaB promoter activity. EGCG and/or IFN also resulted in an increase in Fas-L mediated apoptosis. Further, EGCG and/or IFN treatments resulted in a decrease in melanoma tumor growth and protein levels of proliferation marker PCNA, in athymic nude mice implanted with melanoma tumors. The combination of the two modalities demonstrated a better response than either of them alone. Our data suggest that EGCG could impart therapeutic advantage if used in conjunction with IFN. PMID: 19502799 [PubMed - indexed for MEDLINE] Photomed Laser Surg. 2010 May 3. [Epub ahead of print] Extraordinary Anticancer Effect of Green Tea and Red Light. Sommer AP, Zhu D, Scharnweber T. 1 Institute of Micro and Nanomaterials, University of Ulm , Ulm, Germany . Abstract Abstract Objective: Increasing observational evidence suggests that epigallocatechin gallate-the major polyphenolic component of green tea-is instrumental in suppressing the growth of cancer cells. Therefore, methods that promise to enhance the suppressive potential of green tea have the highest clinical relevance. Background Data: Human cervical cancer cells, HeLa, the first continuous cancer cell line, represent a mainstay model in cancer research. Green tea inhibited their growth, whereas their exposure to moderate levels of laser light resulted in an opposite effect. Both effects are individually documented in the literature. Methods: HeLa cells were supplemented with green tea, irradiated with moderately intense laser light (670 nm) for 1 min, and incubated for 52 h. Results: We found an extraordinary inhibition of HeLa cells by a combination of green tea and red light. We achieved an inhibition of 1,460%, compared with non-irradiated samples. Conclusion: Our result receives clinical relevance from a recent study in which epigallocatechin gallate suppressed the growth of melanoma in vivo. PMID: 20438353 [PubMed - as supplied by publisher] __________________ Mom's treatment history (link)