bcl-2 Protein Inhibits Etoposide-induced Apoptosis through Its Effects on Events Subsequent to Topoisomerase II-induced DNA Strand Breaks and Their Repair

Saori Kamesaki, Hiroshi Kamesaki, Timothy J. Jorgensen, Akihiko Tanizawa, Yves Pommier, Jeffrey Cossman

Research output: Contribution to journalArticle

Abstract

Previous studies have shown that bcl-2 overexpression can inhibit apoptosis induced by DNA-damaging agents widely used in cancer chemotherapy, including X-irradiation, alkylating agents (hydroperoxycyclo-phosphamide, etc.), and topoisomerase II inhibitors (etoposide, etc.). However, little is known about the mechanism by which bcl-2 overexpression inhibits apoptosis triggered by these agents. In this study, we examined whether bcl-2 overexpression could have effects on etoposide-induced DNA damage and its repair. For these experiments, we developed CH31 clones (mouse B-cells) stably transfected with human bcl-2 sense plasmids and compared these clones with a parental CH31 clone or CH31 clones with antisense plasmids. Overexpression of bcl-2 protein inhibited etoposide-induced apoptosis and cytotoxicity. However, there was no or little difference in the production and repair of DNA-protein cross-links, DNA single-strand breaks, and double-strand breaks among a parental CH31 clone and CH31 clones with human bcl-2 sense or antisense plasmids. These findings indicate that (a) apoptosis or cytotoxicity induced by etoposide can be separated into early events (formation of double-strand breaks, DNA single-strand breaks, and double-strand breaks) and later events (secondary DNA fragmentation or cell death) and (b) bcl-2 inhibits apoptosis and cytotoxicity induced by etoposide at some steps between these events.

Original languageEnglish (US)
Pages (from-to)4251-4256
Number of pages6
JournalCancer Research
Volume53
Issue number18
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kamesaki, S., Kamesaki, H., Jorgensen, T. J., Tanizawa, A., Pommier, Y., & Cossman, J. (1993). bcl-2 Protein Inhibits Etoposide-induced Apoptosis through Its Effects on Events Subsequent to Topoisomerase II-induced DNA Strand Breaks and Their Repair. Cancer Research, 53(18), 4251-4256.