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Role of caspase 3-dependent Bcl-2 cleavage in potentiation of apoptosis by Bcl-2.

Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. In the present study, we examine the mechanisms of this effect and demonstrate its relevance for the in vivo situation. Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2-transfected PC12 cells. In contrast, bcl-2 transfection protected PC12 cells from cisplatin-induced apoptosis, and cisplatin treatment did not result in Bcl-2 cleavage. Similarly, Bcl-2 cleavage did not occur and Bcl-2-mediated protection from, rather than potentiation of apoptosis was observed after NCS treatment of MCF-7 breast cancer cells. The caspase 3-specific inhibitor Ac-DEVD-CHO prevented Bcl-2 cleavage and attenuated NCS-induced apoptosis in bcl-2-transfected PC12 cells, whereas it had no effect on NCS-induced apoptosis in mock-transfected PC12 cells. Furthermore, MCF-7 cells do not express caspase 3, a finding in concert with the lack of Bcl-2 cleavage in this line. In in vivo experiments, xenografts of bcl-2-transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells. Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis.

Pubmed ID: 11752215


  • Liang Y
  • Nylander KD
  • Yan C
  • Schor NF


Molecular pharmacology

Publication Data

January 25, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: R01-CA74289

Mesh Terms

  • Animals
  • Antineoplastic Agents
  • Apoptosis
  • Caspase 3
  • Caspase Inhibitors
  • Caspases
  • Cisplatin
  • Cysteine Proteinase Inhibitors
  • Disease Models, Animal
  • Drug Interactions
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Mice, Nude
  • Oligopeptides
  • PC12 Cells
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Transfection
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Zinostatin