绿茶EGCG防癌作用的分子靶点

doi:10.13305/j.cnki.jts.2010.06.002

茶叶科学 ›› 2010, Vol. 30 ›› Issue (6): 414-422.doi: 10.13305/j.cnki.jts.2010.06.002

绿茶EGCG防癌作用的分子靶点

顾成波^1,2,5, 袁肖寒^3,4, 付玉杰^1,2, 祖元刚^1,2,*, 赵恩泽^1,2, 李旺^1,2, 王秋雪^1,2

1. 东北林业大学森林植物生态学教育部重点实验室,黑龙江哈尔滨 150040;
2. 东北林业大学林业生物制剂教育部工程研究中心,黑龙江哈尔滨 150040;
3. 东北林业大学林学院,黑龙江哈尔滨 150040;
4. 东北农业大学生命科学与生物技术研究中心,黑龙江哈尔滨 150030;
5. 浙江海正药业股份有限公司,浙江台州 318000

收稿日期:2010-01-06 修回日期:2010-03-11 发布日期:2019-09-11
通讯作者: zygorl@yahoo.com.cn
作者简介:顾成波（1975— ）,男,黑龙江哈尔滨人,讲师,主要从事药用植物活性成分提取分离及其药理作用研究。
基金资助:
国家科技支撑计划资助项目(2006BAD18B0401),中央高校基本科研业务费专项资金（DL09BA20）,东北林业大学青年科研基金（07030）

Molecular Targets for Cancer Chemoprevention by (-)-Epigallocatechin Gallate of Green Tea

GU Cheng-bo^1,2,5, YUAN Xiao-han^3,4, FU Yu-jie^1,2, ZU Yuan-gang^1,2,*, ZHAO En-ze^1,2, LI Wang^1,2, WANG Qiu-xue^1,2

1. Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China;
2. Engineering Research Center of Forest Bio-preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China;
3. College of Forestry, Northeast Forestry University, Harbin 150040, China;
4. Life Science and Biotechnique Research Center, Northeast Agricultural University, Harbin 150030, China;
5. Zhejiang Hisun Pharmaceutical Co. Ltd, Taizhou 318000, China

Received:2010-01-06 Revised:2010-03-11 Published:2019-09-11

摘要/Abstract

摘要： 表没食子儿茶素没食子酸酯（EGCG）是绿茶中含量最高、活性最强的多酚类成分。近年来绿茶EGCG癌症预防作用的分子靶点一直备受关注。本文对已报道的EGCG癌症预防作用机制及其可能的作用靶点进行了综述,讨论了将EGCG开发为癌症化学预防剂应采取的策略,以期为设计预防癌症的新方案提供借鉴。

关键词: EGCG, 癌症化学预防, 分子机制, 分子靶点

Abstract: (-)-Epigallocatechin gallate (EGCG) is the most active and major polyphenolic compound in green tea. The molecular mechanisms and targets on the action of EGCG have been extensively investigated. This paper reviewed some of the reported mechanisms and possible targets for the action of EGCG, and strategies for cancer chemoprevention by EGCG in clinical trials were discussed. It provides a new inspiration for cancer chemoprevention.

Key words: EGCG, cancer chemoprevention, molecular mechanisms, molecular targets

中图分类号:

TS272
R730.1

顾成波, 袁肖寒, 付玉杰, 祖元刚, 赵恩泽, 李旺, 王秋雪. 绿茶EGCG防癌作用的分子靶点[J]. 茶叶科学, 2010, 30(6): 414-422. doi: 10.13305/j.cnki.jts.2010.06.002.

GU Cheng-bo, YUAN Xiao-han, FU Yu-jie, ZU Yuan-gang, ZHAO En-ze, LI Wang, WANG Qiu-xue. Molecular Targets for Cancer Chemoprevention by (-)-Epigallocatechin Gallate of Green Tea[J]. Journal of Tea Science, 2010, 30(6): 414-422. doi: 10.13305/j.cnki.jts.2010.06.002.

参考文献

[1] Naghma Khan, Farrukh Afaq, Mohammad Saleem, et al. Targeting Multiple Signaling Pathways by Green Tea Polyphenol(-)-Epigallocatechin-3-Gallate[J]. Cancer Res, 2006, 66(5): 2500-2505.
[2] Yang CS, Maliakal P, Meng X.Inhibition of carcinogenesis by tea[J]. Annu Rev Pharmacol Toxicol, 2002(42): 25-54.
[3] Yang CS, Sang S, Lambert JD, et al. Possible mechanisms of the cancer-preventive activities of green tea[J]. Molecular nutrition & food research, 2006, 50(2): 170-175.
[4] Park OJ, Surh YJ.Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies[J]. Toxicol Lett, 2004, 150(1): 43-56.
[5] Yang CS, Wang X, Lu G, et al. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance[J]. Nat Rev Cancer, 2009, 9(6): 429-439.
[6] Moyers SB, Kumar NB.Green tea polyphenols and cancer chemoprevention: multiple mechanisms and endpoints for phase II trials. Nutr Rev 2004, 62(5):204-211.
[7] Yang CS, Landau JM, Huang MT, et al. Inhibition of carcinogenesis by dietary polyphenolic compounds[J]. Annual Review of Nutrition, 2001, 21: 381-406.
[8] Bettuzzi S, Brausi M, Rizzi F, et al. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia:a preliminary report from a one-year proof-of-principle study[J]. Cancer Res, 2006, 66(2): 1234-1240.
[9] Nagle DG, Ferreira D, Zhou YD.Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives[J]. Phytochemistry. 2006, 67(17): 1849-1855.
[10] Tachibana H, Koga K, Fujimura Y, et al. A receptor for green tea polyphenol EGCG[J]. Nat Struct Mol Biol, 2004, 11(4):380-381.
[11] Leone M, Zhai D, Sareth S, et al. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins[J]. Cancer Res, 2003, 63(23): 8118-8121.
[12] Ermakova S, Choi BY, Choi, et al. The intermediate filament protein vimentin is a new target for epigallocatechin gallate[J]. J Biol Chem, 2005, 208(17): 16882-16890.
[13] Katiyar SK, Afaq F, Azizuddin K, et al. Inhibition of UVB-induced oxidative stressmediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (-)-epigallocatechin-3-gallate[J]. Toxicol Appl Pharmacol, 2001, 176(2): 110-117.
[14] Maeda-Yamamoto M, Suzuki N, Sawai Y, et al. Association of suppression of extracellular signal-regulated kinase phosphorylation by epigallocatechin gallate with the reduction of matrix metalloproteinase activities in human fibrosarcoma HT1080 cells[J]. J agric Food Chem, 2003, 51(7): 1858-1863.
[15] Chung JY, Huang C, Meng X.Inhibition of activator protein 1 activity and cell growth by purified green tea polyphones and black tea polyphenols in H-ras-transformed cells:structure-activity relationship and mechanism involved[J]. Cancer Res, 1999, 59(18): 4610-4617.
[16] Hou Z, Lambert JD, Chin KV, et al. Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention[J]. Mutat Res, 2004,555(1/2): 3-19.
[17] Surh YJ, Chun KS, Cha HH. Molecular mechanisms underlying chemoprevention activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappaB activation[J]. Mutat Res, 2001, 480/481: 243-268.
[18] Dong Z, Ma W, Huang C, et al. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate and theaflavins[J]. Cancer Res, 1997, 57(19): 4414-4419.
[19] Huang C, Ma WY, Hanenberger D, et al. Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice[J]. J Biol Chem, 1997, 272(42): 26325-26331.
[20] Liang YC, Lin-Shiau SY, Chen CF, et al. Inhibition of cyclindependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3-gallate[J]. J Cell Biochem, 1999, 75(1): 1-12.
[21] Liang YC, Lin-Shiau SY, Chen CF, et al. Suppression of extracelluar signals and cell proliferation through EGF receptor binding epigallocatechin gallate in human A431 epidemloid carcinoma cells[J]. J Cell Biochem, 1997, 67(1): 55-65.
[22] Sah JF, Balasubramanian S, Eckert RL, et al. Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases[J]. J Biol Chem, 2004, 279(13): 12755-12762.
[23] Masuda M, Suzui M, Lim JT, et al. Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction[J]. J Exp Ther Oncol, 2002, 2(6): 350-359.
[24] Masuda M, Suzui M, Weinstein IB.Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines[J]. Clin Cancer Res, 2001, 7(12): 4220-4229.
[25] Shimizu M, Deguchi A, Lim JT, et al. (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells[J]. Clin Cancer Res, 2005, 11(7): 2735-2746.
[26] Naasani I, Oh-Hara F, Oh-Hara T, et al. Blocking telomerase by dietary polyphenols is a major mechanism for limiting the growth of human cancer cells in vitro and in vivo[J]. Cancer Res, 2003, 63(4): 824-830.
[27] Naasani I, Seimiya H, TsuruoT. Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins[J]. Biochem Biophys Res Commun, 1998, 249(2): 391-396.
[28] Fang MZ, Wang Y, Ai N, et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines[J]. Cancer Res, 2003, 63(22): 7563-7570.
[29] Navarro-Perán E, Cabezas-Herrera J, García-Cánovas F, et al. The antifolate activity of tea catechins[J]. Cancer Res, 2005, 65(6): 2059-2064.
[30] Montagut C, Rovira A, Albanell J.The proteasome: anovel target for anticancer therapy[J]. Clin Transl Oncol, 2006, 8(5):313-317.
[31] Nam S, Smith DM, Dou QP.Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo[J]. J Biol Chem, 2001, 276(16): 13322-13330.
[32] Li M, He Z, Ermakova S,et al. Direct inhibition of insulin-like growth factor-I receptor kinase activity by (-)-epigallocatechin-3-gallate regulates cell transformation[J]. Cancer Epidemiol Biomarkers Prev, 2007, 16(3): 598-605.
[33] He ZW, Tang F, Ermakova S,et al. Fyn is a novel target of (-)-epigallocatechin gallate in the inhibition of JB6 C141 cell transformation[J]. Moi Carcinog, 2008, 47(2): 172-183.
[34] Ermakova SP, Bong SK, Bu YC, et al. (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucose-regulated protein 78[J]. Cancer Res, 2006, 66(18): 9260-9269.
[35] Shim JH, Choi HS, Pugliese A, et al. (-)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinase[J]. J Biol Chem, 2008, 283(42): 28370-28379.
[36] Konstantinopoulos PA, Karamouzis MV, Papatsoris AG, et al. Matrix metalloproteinase inhibitors as anticancer agents[J]. Int J Biochem Cell, 2008, 40(6/7): 1156-1168.
[37] Zhen MC, Huang XH, Wang Q, et al. Green tea polyphenol epigallocatechin-3-gallate suppresses rat hepatic stellate cell invasion by inhibition of MMP-2 expression and its activation[J]. Acta Pharmacol Sin, 2006, 27(12): 1600-1607.
[38] Fassina G, Vene R, Morini M, et al. Mechanisms of inhibition of tumor angiogenesis and vascular tumor growth by epigallocatechin-3-gallate[J]. Clin Cancer Res, 2004, 10(14): 4865-4873.
[39] Ho YC, Yang SF, Peng CY, et al. Epigallocatechin-3-gallate inhibits the invasion of human oral cancer cells and decreases the productions of matrix metalloproteinases and urokinase-plasminogen activator[J]. J Oral Pathol Med, 2007, 36(10): 588-593.
[40] Berger S J, Gupta S, Belfi CA, et al. Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells[J]. Biochem Biophys Res Commun, 2001, 288(1): 101-105.
[41] Hayakawa S, Saeki K, Sazuka M, et al. Apoptosis induction by epigallocatechin gallate involves its binding to Fas[J]. Biochem Biophys Res Commun, 2001, 285(5): 1102-1106.
[42] Brusselmans K, De Schrijver E, Heyns W, et al. Epigallo-catechin-3-gallate is a potent natural inhibitor of fatty acid synthase in intact cells and selectively induces apoptosis in prostate cancer cells[J]. Int J Cancer.2003, 106(6): 856-862.
[43] Jung YD, Kim MS, Shin BA, et al. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells[J]. Br J Cancer, 2001, 84(6): 844-850.
[44] Jankun J, Selman SH, Swiercz R, et al. Why drinking green tea could prevent cancer[J]. Nature, 1997, 387(6633): 561.
[45] Yoshizawa S, Horiuchi T, Fujiki H, et al. Antitumor promoting activity of(-)-epigallocatechin gallate, the main constituent of “tannin” in green tea[J]. Phytother Res, 1987(1): 44-47.
[46] Gupta S, Hastak K, Ahmad N, et al. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols[J]. Proc Natl Acad Sci USA, 2001, 98(18): 10350-10355.
[47] AdhamiVM, Siddiqui IA, AhmadN, et al. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer[J]. Cancer Res, 2004, 64(23): 8715-8722.
[48] Vayalil PK, Elmets CA, Katiyar SK.Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin[J]. Carcinogenesis, 2003 24(5): 927-936.
[49] Liao J, Yang GY, Park ES, et al. Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea[J]. Nutr Cancer, 2004, 48(1): 44-53.
[50] Ju J, Hong J, Zhou JN, et al. Inhibition of intestinal tumorigenesis in Apc^min/+ mice by(-)-epigallocatechin-3-
1)gallate, the major catechin in green tea[J]. Cancer Res, 2005, 65(22): 10623-10631.
[51] Umeda D, Yano S, Yamada K, et al. Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor[J]. J BiolChem, 2008, 283(6): 3050-3058.
[52] Ahn WS, Yoo J, Huh SW, et al. Protective effects of green tea extract (polyphenon E and EGCG) on human cervical lesions[J]. Eur J Cancer Prev, 2003(12): 383-390.
[53] Jatoi A, Ellison N, Burch PA, et al. A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma[J]. Cancer, 2003, 97(6): 1442-1446.
[54] Fujiki H.Two stages of cancer prevention with green tea[J]. J Cancer Res Clin Oncol, 1999, 125(11): 589-597.
[55] Lee WJ, Shim JY, Zhu BT, et al. Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids[J]. Mol.Pharmacol, 2005, 68(4): 1018-1030.
[56] Abe I, Seki T, Umehara K, et al. Green tea polyphenols: novel and potent inhibitors of squalene epoxidase[J]. Biochem Biophys Res Commun, 2000, 268(3): 767-771.
[57] Lamy S, Gingras D, Beliveau R.Green tea catechins inhibit vascular endothelial growth factor receptor phosphorylation[J]. Cancer Res, 2002, 62(2): 381-385.
[58] U Ullmann, J Haller, JP Decourt, et al. A single ascending dose study of EGCg in healthy volunteers[J]. J Int Met Res, 2003, 31(2): 88-101.
[59] RA Isbrucker, JA Edwards, E Wolz, et al. Safety studies on epigallocatechin gallate (EGCG) preparations. Part 3: Teratogenicity and reproductive toxicity studies in rats[J]. Food and Chemical Toxicology, 2006, 44(5): 651-661.
[60] Chung S Y, Joshua DL, Zhe H, et al. Molecular Targets for the Cancer Preventive Activity of Tea Polyphenols[J]. Molecular Carcinogenesis, 2006, 45(6): 431-435.
[61] Li L,Chan TH.Enantioselective synthesis of EGCG, the active polyphenol component from green tea[J]. Org Lett, 2001, 3(5): 739-741.
[62] Surh YJ.Cancer chemoprevention with dietary phytochemicals[J]. Nature Reviews Cancer, 2003, 3(10): 768-780.
[63] Pisters KM, Newman RA, Coldman B, et al. Phase I trial of oral green tea extract in adult patients with solid tumors[J]. J Clin Oncol, 2001, 19(6): 1830-1838.
[64] Shanafelt T D, Call T, Zent C S, et al. Phase I trial of daily oral polyphenon E in patients with asymptomatic rai stage 0 to II chronic lymphocytic leukemia[J]. Journal of clinical oncology, 2009, 27(23): 3808-3814.
[65] Shanafelt T D, Call T, Zent C S, et al. Phase II trial of daily, oral green tea extract in patients with asymptomatic, Rai stage 0-II chronic lymphocytic leukemia (CLL)[J]. Journal of Clinical Oncology, 2010, 28(15-suppl): 6522.
[66] Joshua D Lambert, Shengmin Sang, Chung S Yang.Possible controversy over dietary polyphenols: benefits vs risks[J]. Chem Res Toxicol, 2007, 20(4): 583-585.
[67] Yang CS, Lambert JD, Sang S.Antioxidative and anti-carcinogenic activities of tea polyphenols[J]. Arch Toxicol, 2009, 83(1): 11-21.

绿茶EGCG防癌作用的分子靶点

Molecular Targets for Cancer Chemoprevention by (-)-Epigallocatechin Gallate of Green Tea

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