Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver

The antitumor effect of green tea polyphenols has been well characterized i n numerous papers. However, the mechanism of their action is still poorly d efined. In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea extract, was studied for its effect on the expression of glut athione S-transferases (GSTs) in rat liver to examine the mechanism of acti on. Liver samples were collected from Sprague-Dawley rats created with EGCG in H2O by portal vein perfusion and examined for total GST activity and GS T expression. The results showed that the induction of GST activity by EGCG was dose- and time-dependent. GST activity was increased about 28-fold at 12 hr after treatment. Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 m g/kg weight). Only GSTM2 revealed a significant time-dependent increase, wi th a maximal induction of similar to 2.0-fold. The differential effect of E GCG on GST subunit expression was also verified by immunocytochemical exami nation and showed strong induction of the GSTM2 (but not the GSTA1/2 and GS TM1) level in liver section. This induction occurred as early as 3 hr after treatment and extended gradually outward from the hepatic veins as treatme nt time increased. The change in the GSTM2 protein level was accompanied by a corresponding alteration in mRNA quantity (similar to 2.0-fold of contro l). Our report is the first to demonstrate a specific induction of the GSTM 2 subunit by a chemopreventor and suggests a primary influence of EGCG on G STM2 gene expression. BIOCHEM PHARMACOL 60;5:643-650, 2000. (C) 2000 Elsevi er Science Inc.