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. 2001 Mar;84(6):844–850. doi: 10.1054/bjoc.2000.1691

EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

Y D Jung 1,2, M S Kim 1, B A Shin 1, K O Chay 1, B W Ahn 1, W Liu 2, C D Bucana 2, G E Gallick 2, L M Ellis 2,3
PMCID: PMC2363808  PMID: 11259102

Abstract

Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 μM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day−1mouse−1starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: epigallocatechin gallate (EGCG), vascular endothelial growth factor (VEGF), colon carcinoma, Erk-1, Erk-2, angiogenesis

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Selected References

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  1. Ahmad N., Feyes D. K., Nieminen A. L., Agarwal R., Mukhtar H. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Inst. 1997 Dec 17;89(24):1881–1886. doi: 10.1093/jnci/89.24.1881. [DOI] [PubMed] [Google Scholar]
  2. Ahn H. Y., Hadizadeh K. R., Seul C., Yun Y. P., Vetter H., Sachinidis A. Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172). Mol Biol Cell. 1999 Apr;10(4):1093–1104. doi: 10.1091/mbc.10.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akagi Y., Liu W., Zebrowski B., Xie K., Ellis L. M. Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res. 1998 Sep 1;58(17):4008–4014. [PubMed] [Google Scholar]
  4. Asano Y., Okamura S., Ogo T., Eto T., Otsuka T., Niho Y. Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia. Life Sci. 1997;60(2):135–142. doi: 10.1016/s0024-3205(96)00603-0. [DOI] [PubMed] [Google Scholar]
  5. Cao Y., Cao R. Angiogenesis inhibited by drinking tea. Nature. 1999 Apr 1;398(6726):381–381. doi: 10.1038/18793. [DOI] [PubMed] [Google Scholar]
  6. Cobb M. H., Goldsmith E. J. How MAP kinases are regulated. J Biol Chem. 1995 Jun 23;270(25):14843–14846. doi: 10.1074/jbc.270.25.14843. [DOI] [PubMed] [Google Scholar]
  7. Davis R. J. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem. 1993 Jul 15;268(20):14553–14556. [PubMed] [Google Scholar]
  8. Ellis L. M., Liu W., Wilson M. Down-regulation of vascular endothelial growth factor in human colon carcinoma cell lines by antisense transfection decreases endothelial cell proliferation. Surgery. 1996 Nov;120(5):871–878. doi: 10.1016/s0039-6060(96)80097-3. [DOI] [PubMed] [Google Scholar]
  9. Ellis L. M., Staley C. A., Liu W., Fleming R. Y., Parikh N. U., Bucana C. D., Gallick G. E. Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src. J Biol Chem. 1998 Jan 9;273(2):1052–1057. doi: 10.1074/jbc.273.2.1052. [DOI] [PubMed] [Google Scholar]
  10. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  11. Fujiki H., Suganuma M., Okabe S., Sueoka N., Komori A., Sueoka E., Kozu T., Tada Y., Suga K., Imai K. Cancer inhibition by green tea. Mutat Res. 1998 Jun 18;402(1-2):307–310. doi: 10.1016/s0027-5107(97)00310-2. [DOI] [PubMed] [Google Scholar]
  12. Hibasami H., Komiya T., Achiwa Y., Ohnishi K., Kojima T., Nakanishi K., Akashi K., Hara Y. Induction of apoptosis in human stomach cancer cells by green tea catechins. Oncol Rep. 1998 Mar-Apr;5(2):527–529. doi: 10.3892/or.5.2.527. [DOI] [PubMed] [Google Scholar]
  13. Jankun J., Selman S. H., Swiercz R., Skrzypczak-Jankun E. Why drinking green tea could prevent cancer. Nature. 1997 Jun 5;387(6633):561–561. doi: 10.1038/42381. [DOI] [PubMed] [Google Scholar]
  14. Ji B. T., Chow W. H., Hsing A. W., McLaughlin J. K., Dai Q., Gao Y. T., Blot W. J., Fraumeni J. F., Jr Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer. 1997 Jan 27;70(3):255–258. doi: 10.1002/(sici)1097-0215(19970127)70:3<255::aid-ijc1>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  15. Jung Y. D., Nakano K., Liu W., Gallick G. E., Ellis L. M. Extracellular signal-regulated kinase activation is required for up-regulation of vascular endothelial growth factor by serum starvation in human colon carcinoma cells. Cancer Res. 1999 Oct 1;59(19):4804–4807. [PubMed] [Google Scholar]
  16. Kitano K., Nam K. Y., Kimura S., Fujiki H., Imanishi Y. Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein phosphatase 2A. Biophys Chem. 1997 Apr 22;65(2-3):157–164. doi: 10.1016/s0301-4622(96)02254-5. [DOI] [PubMed] [Google Scholar]
  17. 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. 1997 Oct 1;67(1):55–65. doi: 10.1002/(sici)1097-4644(19971001)67:1<55::aid-jcb6>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  18. Mahadevan D., Thanki N., Aroca P., McPhie P., Yu J. C., Beeler J., Santos E., Wlodawer A., Heidaran M. A. A divalent metal ion binding site in the kinase insert domain of the alpha-platelet-derived growth factor receptor regulates its association with SH2 domains. Biochemistry. 1995 Feb 21;34(7):2095–2106. doi: 10.1021/bi00007a002. [DOI] [PubMed] [Google Scholar]
  19. Milanini J., Viñals F., Pouysségur J., Pagès G. p42/p44 MAP kinase module plays a key role in the transcriptional regulation of the vascular endothelial growth factor gene in fibroblasts. J Biol Chem. 1998 Jul 17;273(29):18165–18172. doi: 10.1074/jbc.273.29.18165. [DOI] [PubMed] [Google Scholar]
  20. Paschka A. G., Butler R., Young C. Y. Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate. Cancer Lett. 1998 Aug 14;130(1-2):1–7. doi: 10.1016/s0304-3835(98)00084-6. [DOI] [PubMed] [Google Scholar]
  21. Rogers A. E., Hafer L. J., Iskander Y. S., Yang S. Black tea and mammary gland carcinogenesis by 7,12-dimethylbenz[a]anthracene in rats fed control or high fat diets. Carcinogenesis. 1998 Jul;19(7):1269–1273. doi: 10.1093/carcin/19.7.1269. [DOI] [PubMed] [Google Scholar]
  22. Sebolt-Leopold J. S., Dudley D. T., Herrera R., Van Becelaere K., Wiland A., Gowan R. C., Tecle H., Barrett S. D., Bridges A., Przybranowski S. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat Med. 1999 Jul;5(7):810–816. doi: 10.1038/10533. [DOI] [PubMed] [Google Scholar]
  23. Stoner G. D., Mukhtar H. Polyphenols as cancer chemopreventive agents. J Cell Biochem Suppl. 1995;22:169–180. doi: 10.1002/jcb.240590822. [DOI] [PubMed] [Google Scholar]
  24. Swiercz R., Skrzypczak-Jankun E., Merrell M. M., Selman S. H., Jankun J. Angiostatic activity of synthetic inhibitors of urokinase type plasminogen activator. Oncol Rep. 1999 May-Jun;6(3):523–526. doi: 10.3892/or.6.3.523. [DOI] [PubMed] [Google Scholar]
  25. Takahashi Y., Bucana C. D., Liu W., Yoneda J., Kitadai Y., Cleary K. R., Ellis L. M. Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. J Natl Cancer Inst. 1996 Aug 21;88(16):1146–1151. doi: 10.1093/jnci/88.16.1146. [DOI] [PubMed] [Google Scholar]
  26. Takahashi Y., Kitadai Y., Bucana C. D., Cleary K. R., Ellis L. M. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res. 1995 Sep 15;55(18):3964–3968. [PubMed] [Google Scholar]
  27. Takahashi Y., Tucker S. L., Kitadai Y., Koura A. N., Bucana C. D., Cleary K. R., Ellis L. M. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer. Arch Surg. 1997 May;132(5):541–546. doi: 10.1001/archsurg.1997.01430290087018. [DOI] [PubMed] [Google Scholar]
  28. Warren R. S., Yuan H., Matli M. R., Gillett N. A., Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest. 1995 Apr;95(4):1789–1797. doi: 10.1172/JCI117857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yang C. S., Wang Z. Y. Tea and cancer. J Natl Cancer Inst. 1993 Jul 7;85(13):1038–1049. doi: 10.1093/jnci/85.13.1038. [DOI] [PubMed] [Google Scholar]
  30. Yu G. P., Hsieh C. C., Wang L. Y., Yu S. Z., Li X. L., Jin T. H. Green-tea consumption and risk of stomach cancer: a population-based case-control study in Shanghai, China. Cancer Causes Control. 1995 Nov;6(6):532–538. doi: 10.1007/BF00054162. [DOI] [PubMed] [Google Scholar]

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