Anticancer and Anti-inflammatory Effects of Cysteine Metabolites of the Green Tea Polyphenol, (−)-Epigallocatechin-3-gallate

Abstract

(−)-Epigallocatechin-3-gallate (EGCG) has been shown to have cancer preventive activity in vitro and in vivo. We have previously shown that EGCG can undergo conjugation to cysteine to form 2′-cysteinyl-EGCG and 2′′-cysteinyl-EGCG. Studies of thiol-conjugated metabolites of methamphetamine indicate that such metabolites are not detoxified but retain biological activity. Here, we examined the growth inhibitory, pro-oxidant, and anti-inflammatory activities of the cysteine metabolites of EGCG. Both compounds dose-dependently inhibited the growth of colon cancer and intestinal cell lines. Both metabolites prevented aberrant arachidonic acid release and nitric oxide production by lipopolysaccharide-stimulated RAW264.7 cells. Under cell culture conditions, 2′′-cysteinyl-EGCG produced H2O2 at a faster rate than EGCG. The results of the present study show that cysteine conjugates of EGCG retain the growth inhibitory, anti-inflammatory, and pro-oxidant activities of EGCG in vitro and may play a role in disease prevention in vivo. These results remain to be confirmed in vivo.