Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance

Nature Reviews Cancer

Volumn 9, Issue 6, 2009, Pages 429-439

  Yang, Chung S ^a,b   Wang, Xin ^a,b   Lu, Gang ^a,b   Picinich, Sonia C ^a,b  

^a RUTGERS UNIVERSITY   (United States)

^b RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; BLACK TEA EXTRACT; CAFFEINE; CATECHIN; EPICATECHIN; EPICATECHIN GALLATE; EPIGALLOCATECHIN; EPIGALLOCATECHIN GALLATE; GREEN TEA EXTRACT; PLANT MEDICINAL PRODUCT; POLYPHENOL DERIVATIVE; POLYPHENON B; POLYPHENON E; THEAFLAVIN; THEAFLAVIN 3,3' DIGALLATE; THEAFLAVINE 3 GALLATE; THEAFLAVINE 3' GALLATE; THEARUBIGIN DERIVATIVE; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; PLANT EXTRACT; TEA;

ANGIOGENESIS; ANTIOXIDANT ACTIVITY; ARTICLE; BIOCHEMICAL COMPOSITION; BIOLOGICAL ACTIVITY; BLADDER CANCER; BREAST CANCER; CANCER PREVENTION; CANCER RISK; CARCINOGENESIS; CLINICAL TRIAL; COLON ADENOCARCINOMA; COLON CANCER; COLORECTAL CARCINOMA; DIGESTIVE SYSTEM TUMOR; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME ACTIVITY; ESOPHAGUS CANCER; FOOD INTAKE; HUMAN; INTESTINE TUMOR; LIVER CANCER; LUNG ADENOCARCINOMA; LUNG ADENOMA; LUNG CANCER; LUNG TUMOR; MOUTH CANCER; MOUTH TUMOR; NONHUMAN; OXIDATION; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE ADENOCARCINOMA; PROSTATE CANCER; PROSTATE TUMOR; PROSTATIC INTRAEPITHELIAL NEOPLASIA; RISK REDUCTION; SKIN CANCER; SMALL INTESTINE CANCER; STOMACH CANCER; TEA; THYROID CANCER; ANALOGS AND DERIVATIVES; ANIMAL; CHEMISTRY; NEOPLASMS; PHYTOTHERAPY;

ANIMALS; ANTICARCINOGENIC AGENTS; CATECHIN; HUMANS; NEOPLASMS; PHYTOTHERAPY; PLANT EXTRACTS; TEA;

EID: 67649449180     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2641     Document Type: Article

References (120)

1. Yang, C. S. & Wang, Z. Y. Tea and cancer. J. Natl Cancer Inst. 85, 1038-1049(1993).
2. Bushman, J. L. Green tea and cancer in humans: a review of the literature. Nutr. Cancer 31, 151-159 (1998).
3. Yang, C. S., Maliakal, P. & Meng, X. Inhibition of carcinogenesis by tea. Annu. Rev. Pharmacol. Toxicol. 42, 25-54 (2002).
4. Hou, Z., Lambert, J. D., Chin, K. V. & Yang, C. S. Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention. Mutat. Res. 555, 3-19 (2004).
5. Lambert, J. D., Hong, J., Yang, G. Y., Liao, J. & Yang, C. S. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am. J. Clin. Nutr. 81, 284S-291S (2005).
6. Clark, J. & You, M. Chemoprevention of lung cancer by tea. Mol. Nutr. Food Res. 50, 144-151 (2006).
7. Khan, N., Afaq, F., Saleem, M., Ahmad, N. & Mukhtar, H. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3- gallate. Cancer Res. 66, 2500-2505 (2006).
8. Wu, A. H. & Yu, M. C. Tea, hormone-related cancers and endogenous hormone levels. Mol. Nutr. Food Res. 50, 160-169(2006).
9. Yang, C. S. et al. Possible mechanisms of the cancer-preventive activities of green tea. Mol. Nutr. Food Res. 50, 170-175(2006).
10. Ju, J.,Lu, G., Lambert, J. D. &Yang, C. S. Inhibition of carcinogenesis by tea constituents. Semin. Cancer Biol. 17, 395-402(2007).
11. Balentine, D. A., Wiseman, S. A. & Bouwens, L. C. The chemistry of tea flavonoids. Crit. Rev. Food Sci. Nutr. 37, 693-704 (1997). This is a comprehensive review of the composition of different types of tea and the chemistry of tea constituents.
12. Valcic, S., Burr, J. A., Timmermann, B. N. & Liebler, D. C. Antioxidant chemistry of green tea catechins. New oxidation products of (-)-epigallocatechin gallate and (-)-epigallocatechin from their reactions with peroxyl radicals. Chem. Res. Toxicol. 13, 801-810 (2000).
13. Sang, S. M. et al. Theadibenzotropolone A, a new type pigment from enzymatic oxidation of (-)-epicatechin and (-)-epigallocatechin gallate and characterized from black tea using LC/MS/MS. Tetrahedron Lett. 43, 7129-7133 (2002).
14. Hou, Z. et al. Mechanism of action of (-)-epigallocatechin-3- gallate: auto-oxidation-dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells. Cancer Res. 65, 8049-8056 (2005).
15. Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3-26(2001).
16. Lee, M. J. et al. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol. Biomarkers Prev. 11, 1025-1032 (2002).
17. Chow, H. H.et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin. Cancer Res. 9, 3312-3319 (2003).
18. Chow, H. H.et al. Effects of dosing condition on the oral bioavailability of green tea catechins after singledose administration of polyphenon E in healthy individuals. Clin. Cancer Res. 11, 4627-4633 (2005).
19. Chen, L., Lee, M. J., Li, H. &Yang, C. S. Absorption, distribution, elimination of tea polyphenols in rats. DrugMetab. Dispos. 25, 1045-1050(1997).
20. Lambert, J. D. et al. Dose-dependent levels of epigallocatechin-3-gallate in human colon cancer cells and mouse plasma and tissues. Drug Metab. Dispos. 34, 8-11 (2006).
21. Yang, C. S., Sang, S., Lambert, J. D. & Lee, M. J. Bioavailability issues in studying the health effects of plant polyphenolic compounds. Mol. Nutr. Food Res. 52 (Suppl. 1), 139-151 (2008).
22. Wang, Z. Y. et al. Inhibition of N-nitrosodiethylamine-and 4-(methylnitrosamino)-1 -(3-pyridyl)-1 -butanoneinduced tumorigenesis in A/J mice by green tea and black tea. Cancer Res. 52, 1943-1947 (1992).
23. Xu, Y., Ho, C. T., Amin, S. G., Han, C. & Chung, F. L. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res. 52, 3875-3879 (1992).
24. Yang, G. Y. et al. Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1 -(3-pyridyl)-1 -butanone (NNK)-induced lung tumorigenesis in A/J mice. Carcinogenesis 18, 2361-2365 (1997).
25. Chung, F. L. et al. Inhibition of lung carcinogenesis by black tea in Fischer rats treated with a tobacco-specific carcinogen: caffeine as an important constituent. Cancer Res. 58, 4096-4101 (1998).
26. Mimoto, J. et al. (-)-Epigallocatechin gallate can prevent cisplatin-induced lung tumorigenesis in A/J mice. Carcinogenesis 21, 915-919 (2000).
27. Zhang, Z. et al. A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. Cancer Res. 60, 901 -907 (2000).
28. Liao, J. et al. Inhibition of lung carcinogenesis and effects on angiogenesis and apoptosis in A/J mice by oral administration of green tea. Nutr. Cancer 48, 44-53 (2004).
29. Schuller, H. M., Porter, B., Riechert, A., Walker, K. & Schmoyer, R. Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers. Lung Cancer 45, 11 -18 (2004).
30. Lu, G. et al. Inhibition of adenoma progression to adenocarcinoma in a4-(methylnitrosamino)-l-(3-pyridyl)-1 -butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res. 66, 11494-11501 (2006).
31. Landau, J. M., Wang, Z. Y., Yang, G. Y., Ding, W. & Yang, C. S. Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea. Carcinogenesis 19, 501 -507 (1998).
32. Sazuka, M., Murakami, S., Isemura, M., Satoh, K. & Nukiwa, T. Inhibitory effects of green tea infusion on in vitro invasion and in vivo metastasis of mouse lung carcinoma cells. Cancer Lett. 98, 27-31 (1995).
33. Lu, G. et al. Synergistic inhibition of lung tumorigenesis by a combination of green tea polyphenols and atorvastatin. Clin. Cancer Res. 14, 4981 -4988 (2008).
34. Lu, Y. et al. A gene expression signature that can predict green tea exposure and chemopreventive efficacy of lung cancer in mice. Cancer Res. 66, 1956-1963 (2006).
35. Li, N. et al. Inhibition of 7,12-dimethylbenz[a] anthracene (DMBA)-induced oral carcinogenesis in hamsters by tea and curcumin. Carcinogenesis 23, 1307-1313 (2002).
36. Wang, Z. Y. et al. Inhibition of A/-nitrosomethylbenzylamine- induced esophageal tumorigenesis in rats by green and black tea. Carcinogenesis 16, 2143-2148 (1995).
37. Yamane, T. et al. Inhibition of N-methyl-N-nitro- N-nitrosoguanidine-induced carcinogenesis by (-)-epigallocatechin gallate in the rat glandular stomach. Cancer Res. 55, 2081-2084 (1995).
38. Murugan, R. S. et al. Modulatory effects of black tea polyphenols on oxidant-antioxidant profile and expression of proliferation, apoptosis, and angiogenesis-assodated proteins in the rat forestomach carcinogenesis model. J. Gastroenterol. 42, 352-361 (2007).
39. min/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea. Cancer Res. 65, 10623-10631 (2005).
40. min/+ mice by green tea polyphenols (polyphenon E) and individual catechins. Nutr. Cancer 59, 62-69 (2007).
41. Xiao, H. et al. Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethanetreated F344 rats. Carcinogenesis 29, 113-119 (2008).
42. Carter, O. et al. Comparison of white tea, green tea, epigallocatechin-3-gallate, and caffeine as inhibitors of PhlP-induced colonic aberrant crypts. Nutr. Cancer 58, 60-65 (2007).
43. Wang, R. et al. Protective versus promotional effects of white tea and caffeine on PhlP-induced tumorigenesis and β-catenin expression in the rat. Carcinogenesis 29, 834-839 (2008).
44. Liao, S., Umekita, Y., Guo, J., Kokontis, J. M. & Hiipakka, R. A. Growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate. Cancer Lett. 96, 239-243 (1995).
45. Gupta, S., Hastak, K., Ahmad, N., Lewin, J. S. & Mukhtar, H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc. NatlAcad. Sci. USA 98, 10350-10355 (2001).
46. Adhami, V. M., Siddiqui, I. A., Ahmad, N., Gupta, S. & Mukhtar, H. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-l-induced signaling in an autochthonous mouse model of prostate cancer. Cancer Res. 64, 8715-8722 (2004).
47. Gao, Y. T. et al. Reduced risk of esophageal cancer associated with green tea consumption. J. Natl. Cancer Inst. 86, 855-858 (1994).
48. Fujiki, H., Suganuma, M., Imai, K. & Nakachi, K. Green tea: cancer preventive beverage and/or drug. Cancer Lett. 188, 9-13 (2002).
49. Zhang, M., Holman, C. D., Huang, J. P. & Xie, X. Green tea and the prevention of breast cancer: a case-control study in Southeast China. Carcinogenesis 28, 1074-1078 (2007).
50. Sun, C. L. et al. Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China. Carcinogenesis 23, 1497-1503 (2002).
51. Yuan, J. M., Gao, Y. T., Yang, C. S. & Yu, M. C. Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study. Int. J. Cancer 120, 1344-1350(2007).
52. Sasazuki, S., Inoue, M., Miura, T., Iwasaki, M. & Tsugane, S. Plasma tea polyphenols and gastric cancer risk: a case-control study nested in a large population-based prospective study in Japan. Cancer Epidemiol. Biomarkers Prev. 17, 343-351 (2008).
53. Wu, A. H.,Yu, M. C., Tseng, C. C., Hankin, J. & Pike, M. C. Green tea and risk of breast cancer in Asian Americans. Int. J. Cancer 106, 574-579 (2003).
54. Wu, A. H., Tseng, C. C., Van Den Berg, D. &Yu, M. C. Tea intake, COMT genotype, and breast cancer in Asian-American women. CancerRes. 63, 7526-7529 (2003).
55. Bonner, M. R. et al. Green tea consumption, genetic susceptibility, PAH-rich smoky coal, and the risk of lung cancer. Mutat. Res. 582, 53-60 (2005).
56. Li, N., Sun, Z., Han, C. & Chen, J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proc. Soc. Exp. Biol. Med. 220, 218-224 (1999).
57. Ahn, W. S. et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur. J. Cancer Prev. 12, 383-390 (2003).
58. Bettuzzi, S. 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. Cancer Res. 66, 1234-1240 (2006).
59. Shimizu, M.et al. Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol. Biomarkers Prev. 17, 3020-3025 (2008).
60. Conney, A. H. et al. Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice. Toxicol. Appl. Pharmacol. 224, 209-213 (2007).
61. Srividhya, R., Jyothilakshmi, V., Arulmathi, K., Senthilkumaran, V. & Kalaiselvi, P. Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Int. J. Dev. Neurosci. 26, 217-223 (2008).
62. Senthil Kumaran,V., Arulmathi, K., Srividhya, R. & Kalaiselvi, P. Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats. Exp. Gerontol. 43, 176-183 (2008).
63. Higdon, J. V. & Frei, B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit. Rev. Food Sci. Nutr. 43, 89-143 (2003).
64. Inami, S. et al. Tea catechin consumption reduces circulating oxidized low-density lipoprotein. Int. Heart J. 48, 725-732 (2007).
65. Hsu, S. P. et al. Chronic green tea extract supplementation reduces hemodialysis-enhanced production of hydrogen peroxide and hypochlorous acid, atherosclerotic factors, and proinflammatory cytokines. Am. J. Clin. Nutr. 86, 1539-1 547 (2007).
66. Hakim, I. A. et al. Effect of increased tea consumption on oxidative DNA damage among smokers: a randomized controlled study. J. Nutr. 133, 3303S-3309S (2003).
67. Schwartz, J. L., Baker, V., Larios, E. & Chung, F. L. Molecular and cellular effects of green tea on oral cells of smokers: a pilot study. Mol. Nutr. Food Res. 49, 43-51 (2005).
68. Yang, G. Y., Liao, J., Kim, K., Yurkow, E. J. & Yang, C. S. Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19, 611 -616 (1998).
69. Na, H. K. & Surh, Y. J. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem. Toxicol. 46, 1271-1278 (2008).
70. Shen, G. et al. Comparison of (-)-epigallocatechin-3-gallate elicited liver and small intestine gene expression profiles between C57BL/56J mice and C57BL/6J/Nrf2 (-/-) mice. Pharm. Res. 22, 1805-1820 (2005).
71. Chow, H. H. et al. Modulation of human glutathione S-transferases by polyphenon E intervention. Cancer Epidemiol. Biomarkers Prev. 16, 1662-1666 (2007).
72. Tang, L. et al. Modulation of aflatoxin biomarkers in human blood and urine by green tea polyphenols intervention. Carcinogenesis 29, 411-417 (2008).
73. Bonkovsky, H. L. Hepatotoxicity associated with supplements containing Chinese green tea (Camellia sinensis). Ann. Intern. Med. 144, 68-71 (2006).
74. Lambert, J. D., Sang, S. & Yang, C. S. Possible controversy over dietary polyphenols: benefits vs risks. Chem. Res. Toxicol. 20, 583-585 (2007).
75. Tachibana, H., Koga, K., Fujimura, Y. & Yamada, K. A receptor for green tea polyphenol EGCG. Nature Struct. Mol. Biol. 11, 380-381 (2004).
76. Umeda, D., Yano, S., Yamada, K. & Tachibana, H. Green tea polyphenol epigallocatechin-3-gallate signaling pathway through 67-kDa laminin receptor. J. Biol. Chem. 283, 3050-3058 (2008).
77. Leone, M. et al. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. CancerRes. 63, 8118-8121 (2003).
78. Ermakova, S. et al. The intermediate filament protein vimentin is a new target for epigallocatechin gallate. J. Biol. Chem. 280, 16882-16890 (2005).
79. Li, M. et al. Direct inhibition of insulin-like growth factor-l receptor kinase activity by (-)-epigallocatechin-3-gallate regulates cell transformation. Cancer Epidemiol. Biomarkers Prev. 16, 598-605 (2007).
80. He, Z. et al. Fyn is a novel target of (-)-epigallocatechin gallate in the inhibition of JB6 C141 cell transformation. Mol. Carcinog. 47, 172-183 (2008).
81. Ermakova, S. P. et al. (-)-Epigallocatechin gallate overcomes resistance to etoposide-induced cell death by targeting the molecular chaperone glucoseregulated protein 78. Cancer Res. 66, 9260-9269 (2006).
82. Shim, J. H. et al. (-)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinase. J. Biol. Chem. 283, 28370-28379 (2008).
83. Mitsiades, C. S. et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell 5, 221 -230 (2004).
84. Shimizu, M., Deguchi, A., Hara, Y., Moriwaki, H. & Weinstein, I. B. EGCG inhibits activation of the insulinlike growth factor-1 receptor in human colon cancer cells. Biochem. Biophys. Res. Commun. 334, 947-953 (2005).
85. Vittal, R. et al. Gene expression changes induced by green tea polyphenol (-)-epigallocatechin-3-gallate in human bronchial epithelial 21BES cells analyzed by DNA microarray. Mol. CancerTher. 3, 1091-1099 (2004).
86. Kuzuhara, T., Sei, Y., Yamaguchi, K., Suganuma, M. & Fujiki, H. DNA and RNA as new binding targets of green tea catechins. J. Biol. Chem. 281, 17446-17456(2006).
87. Dong, Z., Ma, W., Huang, C. &Yang, C. S. Inhibition of tumor promoter-induced activator protein 1 activation and cell transformation by tea polyphenols, (-)-epigallocatechin gallate, and theaflavins. Cancer Res. 57, 4414-4419 (1997).
88. Chung, J. Y., Huang, C., Meng, X., Dong, Z. & Yang, C. S. Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: structureactivity relationship and mechanisms involved. Cancer Res. 59, 4610-4617 (1999).
89. Chung, J. Y., Park, J. O., Phyu, H., Dong, Z. & Yang, C. S. Mechanisms of inhibition of the Ras-MAP kinase signaling pathway in 30.7b Ras 12 cells by tea polyphenols (-)-epigallocatechin-3-gallate and theaflavin-3,3′-digallate. FASEBJ. 15, 2022-2024 (2001).
90. Liang, Y. C., Lin-Shiau, S. Y., Chen, C. F. & Lin, J. K. Inhibition of cyclin-dependent 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. Cell Biochem. 75, 1 -12 (1999).
91. Nam, S., Smith, D. M. & Dou, Q. P. Ester bondcontaining tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J. Biol. Chem. 276, 13322-13330 (2001).
92. Gupta, S., Ahmad, N., Nieminen, A. L. & Mukhtar, H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (-)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol. Appl. Pharmacol. 164, 82-90 (2000).
93. Gupta, S., Hussain,T. & Mukhtar, H. Molecular pathway for (-)-epigallocatechin-3-gallate-induced cell cycle arrest and apoptosis of human prostate carcinoma cells. Arch. Biochem. Biophys. 410, 177-185 (2003).
94. Smith, D. M.et al. Synthetic analogs of green tea polyphenols as proteasome inhibitors. Mol. Med. 8, 382-392 (2002).
95. Garbisa, S. et al. Tumor invasion: molecular shears blunted by green tea. Nature Med. 5, 1216 (1999).
96. Garbisa, S. et al. Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate. Cancer 91, 822-832 (2001).
97. Annabi, B. et al. Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells. Biochim. Biophys. Acta 1542, 209-220 (2002).
98. Taniguchi, S. et al. Effect of (-)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines. Cancer Lett. 65, 51-54 (1992).
99. Fang, M. Z. et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63, 7563-7570 (2003).
100. Navarro-Peran, E. et al. The antifolate activity of tea catechins. Cancer Res. 65, 2059-2064 (2005).
101. +- competitive inhibitors of glucose-6-phosphate dehydrogenase and other enzymes that employ NADP+ as a coenzyme. Bioorg. Med. Chem. 16, 3580-3586 (2008).
102. Ishii,T. et al. Covalent modification of proteins by green tea polyphenol (-)-epigallocatechin-3-gallate through autoxidation. Free Radic. Biol. Med. 45, 1384-1394 (2008).
103. Lo, H. W. &Hung, M. C. Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival. Br. J. Cancer 94, 184-188 (2006).
104. Liang, Y. C., Lin-shiau, S. Y., Chen, C. F. & Lin, J. K. Suppression of extracellular signals and cell proliferation through EGF receptor binding by (-)-epigallocatechin gallate in human A431 epidermoid carcinoma cells. J. Cell Biochem. 67, 55-65 (1997).
105. Shimizu, M. 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. Clin. Cancer Res. 11, 2735-2746 (2005).
106. Adachi, S. et al. The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT 29 colon cancer cells. Cancer Res. 67, 6493-6501 (2007).
107. Adachi, S. et al. (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells. Carcinogenesis 29, 1986-1993 (2008).
108. Masuda, M. 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. Exp. Ther. Oncol. 2, 350-359 (2002).
109. Peschard, P. & Park, M. From Tpr-Met to Met, tumorigenesis and tubes. Oncogene 26, 1276-1285 (2007).
110. Birchmeier, C., Birchmeier, W., Gherardi, E. & Vande Woude, G. F. Met, metastasis, motility and more. Nature Rev. Mol. Cell Biol. 4, 915-925 (2003).
111. Bigelow, R. L. & Cardelli, J. A. The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene 25, 1922-1930 (2006).
112. Lim, Y. C. et al. (-)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells. Cancer Lett. 271, 140-152 (2008).
113. Sartippour, M. R. et al. Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells. J. Nutr. 132, 2307-2311 (2002).
114. Rodriguez, S. K. et al. Green tea catechin, epigallocatechin-3- gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex. Int. J. Cancer 118, 1635-1644(2006).
115. Zhu, B. H. et al. (-)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF production and angiogenesis. World J. Gastroenterol. 13, 1162-1169 (2007).
116. Sukhthankar, M. et al. A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer. Gastroenterology 134, 1972-1980 (2008).
117. Ciardiello, F. et al. Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor. Clin. Cancer Res. 7, 1459-1465 (2001).
118. Weinstein, I. B. & Joe, A. Oncogene addiction. Cancer Res. 68, 3077-3080; discussion 3080 (2008).
119. Stoner, G. D. et al. Cancer prevention with freeze-dried berries and berry components. Semin. Cancer Biol. 17, 403-410 (2007).
120. Shumway, B. S. et al. Effects of a topically applied bioadhesive berry gel on loss of heterozygosity indices in premalignant oral lesions. Clin. Cancer Res. 14, 2421-2430 (2008).