Cell line dependence of Bcl-2-induced alteration of glutathione handling

N. F. Schor, C. M. Rudin, A. R. Hartman, C. B. Thompson, Y. Y. Tyurina, V. E. Kagan

Research output: Contribution to journalArticlepeer-review

Abstract

Bcl-2 has been associated with both oxidative and antioxidative effects in vivo. Moreover, despite evidence that Bcl-2 is antiapoptotic by virtue of its effect on reactive oxygen species and their scavengers, Bcl-2 exerts its antiapoptotic effects even under anaerobic conditions. The reasons for the variable relationship between Bcl-2 and reactive oxygen species are not clear. The present studies demonstrate that the impact of Bcl-2 on glutathione (GSH) metabolism is cell line-dependent. Bcl-2 overproduction in PC12 cells is associated with increased functional thiol reserves, increased reductive activation of chemotherapeutic prodrugs, and GSH accumulation after treatment with N-acetylcysteine. In contrast, Bcl-2-overproducing MCF-7 breast cancer cells demonstrate neither altered GSH handling nor potentiation of chemotherapeutic prodrug reduction. These findings indicate that the effects of Bcl-2 on GSH handling are millieu-dependent. This could account for the variable effects of Bcl-2 in in vivo systems. Furthermore, since our previous studies have demonstrated that reduction-dependent prodrugs may be useful chemotherapeutic agents against tumors that demonstrate altered GSH handling, screening in vitro for alteration of GSH handling may predict responsiveness of such tumors to these reduction-dependent agents.

Original languageEnglish (US)
Pages (from-to)472-476
Number of pages5
JournalOncogene
Volume19
Issue number3
StatePublished - Jan 20 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Glutathione
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Fingerprint

Dive into the research topics of 'Cell line dependence of Bcl-2-induced alteration of glutathione handling'. Together they form a unique fingerprint.

Cite this