Methylated-(3′′)-Epigallocatechin Gallate Analog Suppresses Tumor Growth in Huh7 Hepatoma Cells Via Inhibition of Angiogenesis

Abstract

It is agreed that many of the antitumor effects of (-)-epigallocatechin gallate (EGCG) are mediated by various other effects. We report a new finding, namely, the antiproliferation potential and mechanism of methylated-(3′′)-epigallocatechin gallate analog (MethylEGCG) having a stronger anti-oxidation effect than EGCG. MethylEGCG inhibited activity of vascular endothelial growth factor (VEGF)-depended VEGF receptor 2 and p42/44 MAPK, cell proliferation, and tube formation in human umbilical vascular endothelial cells (HUVECs) at 1 μ M. Even low- dose (1.1 mg/kg i.p. 8.3 mg/kg p.o.) administration suppressed tumor growth in xenografted Huh7 hepatoma mice by 50%. CD31 positive cells, visualized in blood vessels, were reduced in tumors by 18%, suggesting high antitumor activity via inhibition of angiogenesis. This study indicated that the modification of the 3′′ position methylation of EGCG (MethylEGCG) could reduce cell growth effects at a low concentration in vivo.

ACKNOWLEDGMENTS

We thank Ms. Masako Shinkawa for her expert technical assistance. This study was supported by grant No. 19590757 from the Ministry of Education, Science, Sports and Culture of Japan.