Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green tea

Abstract

Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent.

Figure 1

Chemical structure of green tea catechins.

Figure 2

Effect of EGCG on tumour volume and weight in mice bearing human colon carcinoma cells. Nude mice were inoculated with HT29 cells into the subcutis and treated with EGCG or EC (negative control). EGCG inhibited tumour volume by 61% (a) and tumour weight by 58% (b) relative to tumours from mice treated with EC. Bars indicate standard error of the mean. *P < 0.05 (10 mice per group). (Reproduced with permission from Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE &amp; Ellis LM. (2001) EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. British Journal of Cancer, 84, 844–850).

Figure 3

EGCG inhibits tumour vascularity and tumour cell proliferation. Nude mice were inoculated with HT29 cells into the subcutis and treated with EGCG or EC (negative control). Immunohistochemical staining of tumour sections for CD31 and proliferating cell nuclear antigen (PCNA) was used to quantify tumour vessels and tumour cell proliferation. EGCG inhibited tumour vascularity by 30% and tumour cell proliferation by 27% (a). Immunofluorescent double staining of tumour sections for CD31 and TdT-mediated dUTP nick-end labelling (TUNEL) were performed to quantify the percentages of tumour and endothelial cells undergoing apoptosis. EGCG treatment significantly increased apoptosis of both cell types over that of controls (b). HPF, high-power field. Bars indicate standard error of the mean. *P < 0.05, **P < 0.001 (10 mice per group). (Reproduced with permission from Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE &amp; Ellis LM. (2001) EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. British Journal of Cancer, 84, 844–850).