Involvement of caspase-3 in epigallocatechin-3-gallate-mediated apoptosis of human chondrosarcoma cells.
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.
Islam
S
S
Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland Ohio 44106, USA.
Islam
N
N
Kermode
T
T
Johnstone
B
B
Mukhtar
H
H
Moskowitz
R W
RW
Goldberg
V M
VM
Malemud
C J
CJ
Haqqi
T M
TM
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
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases