title: Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells.
abstract: Green tea polyphenol-(-)epigallocatechin-3-gallate (EGCG)-is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In this study we describe a novel observation that EGCG displayed strong inhibitory effects on the proliferation and viability of HTB-94 human chondrosarcoma cells in a dose-dependent manner and induced apoptosis. Investigation of the mechanism of EGCG-induced apoptosis revealed that treatment with EGCG resulted in DNA fragmentation, induction of caspase-3/CPP32 activity, and cleavage of the death substrate poly(ADP-ribose)polymerase (PARP). Pretreatment of cells with a synthetic pan-caspase inhibitor (Z-VAD-FMK) and a caspase-3-specific inhibitor (DEVD-CHO) prevented EGCG-induced PARP cleavage. The induction of apoptosis by EGCG via activation of caspase-3/CPP32-like proteases may provide a mechanistic explanation for its antitumor effects.
authors.affiliation: Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland Ohio 44106, USA.
authors.forename: S
authors.initials: S
authors.lastname: Islam
authors.forename: N
authors.initials: N
authors.lastname: Islam
authors.forename: T
authors.initials: T
authors.lastname: Kermode
authors.forename: B
authors.initials: B
authors.lastname: Johnstone
authors.forename: H
authors.initials: H
authors.lastname: Mukhtar
authors.forename: R W
authors.initials: RW
authors.lastname: Moskowitz
authors.forename: V M
authors.initials: VM
authors.lastname: Goldberg
authors.forename: C J
authors.initials: CJ
authors.lastname: Malemud
authors.forename: T M
authors.initials: TM
authors.lastname: Haqqi
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001859:Bone Neoplasms; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002813:Chondrosarcoma; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases