Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells

Green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG)-is a potent chemo preventive agent in many test systems and has been shown to inhibit tumor p romotion and induce apoptosis. In this study we describe a novel observatio n that EGCG displayed strong inhibitory effects on the proliferation and vi ability of HTB-94 human chondrosarcoma cells in a dose-dependent manner and induced apoptosis. Investigation of the mechanism of EGCG-induced apoptosi s revealed that treatment with EGCG resulted in DNA fragmentation, inductio n of caspase-3/CPP32 activity, and cleavage of the death substrate poly(ADP -ribose)polymerase (PARP). Pretreatment of cells with a synthetic pan-caspa se inhibitor (Z-VAD-FMK) and a caspase-3-specific inhibitor (DEVD-CHO) prev ented EGCG-induced PARP cleavage. The induction of apoptosis by EGCG via ac tivation of caspase-3/CPP32-like proteases may provide a mechanistic explan ation for its antitumor effects, (C) 2000 Academic Press.