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

Biochem Biophys Res Commun. 2000 Apr 21;270(3):793-7. doi: 10.1006/bbrc.2000.2536.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Bone Neoplasms
  • Caspase 3
  • Caspases / metabolism*
  • Catechin / analogs & derivatives*
  • Catechin / toxicity
  • Cell Survival / drug effects
  • Chondrosarcoma
  • Cysteine Proteinase Inhibitors / pharmacology
  • Humans
  • Kinetics
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cysteine Proteinase Inhibitors
  • Catechin
  • epigallocatechin gallate
  • CASP3 protein, human
  • Caspase 3
  • Caspases