A number of epidemiological, clinical, and experimental researches have indicated that administration of green tea appears to have anti-cancer activity. According to findings of laboratory cell culture studies, a diverse mechanism has been observed underlying the effects of green tea catechins against cancer. These mechanisms include anti-oxidant activity, cell cycle regulation, receptor tyrosine kinase pathway inhibition, immune system modulation, and epigenetic modification control. This review discusses the results of these studies to provide more insight into the effects of green tea administration on cancers observed to date in this research field.

The receptor tyrosine kinase vascular endothelial growth factor (VEGF) receptor (VEGFR) plays an important role in tumor angiogenesis of hepatocellular carcinoma (HCC). (–)‐Epigallocatechin gallate (EGCG), the major biologically active component of green tea, inhibits growth in a variety of human cancer cells by inhibiting the activation of several types of receptor tyrosine kinases. In this study, we examined the effects of EGCG on the activity of the VEGF–VEGFR axis in human HCC cells. The levels of total and phosphorylated (i.e. activated) form of VEGFR‐2 protein (p‐VEGFR‐2) were observed to increase in a series of human HCC cell lines in comparison to the Hc normal human hepatocytes. EGCG preferentially inhibited the growth of HuH7 HCC cells, which express constitutive activation of the VEGF–VEGFR axis, in comparison to Hc cells. Treatment of HuH7 cells with EGCG caused a time‐ and dose‐dependent decrease in the expression of VEGFR‐2 and p‐VEGFR‐2 proteins. The production of VEGF from HuH7 cells was reduced by treatment with EGCG. Drinking of EGCG significantly inhibited the growth of HuH7 xenografts in nude mice and this was associated with inhibition of the activation of VEGFR‐2 and its related downstream signaling molecules, including ERK and Akt. EGCG drinking also decreased the expression of Bcl‐x_L protein and VEGF mRNA in the xenografts. These findings suggest that EGCG can exert, at least in part, its growth‐inhibitive effect on HCC cells by inhibiting the VEGF–VEGFR axis. EGCG might therefore be useful in the treatment of HCC. (Cancer Sci 2009; 100: 1957–1962)