Document Detail

Cell line dependence of Bcl-2-induced alteration of glutathione handling.
MedLine Citation:
PMID:  10656697     Owner:  NLM     Status:  MEDLINE    
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.
N F Schor; C M Rudin; A R Hartman; C B Thompson; Y Y Tyurina; V E Kagan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oncogene     Volume:  19     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-02-10     Completed Date:  2000-02-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  472-6     Citation Subset:  IM    
Department of Pediatrics, University of Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
Acetylcysteine / pharmacology
Breast Neoplasms / metabolism
Glutathione / metabolism*
PC12 Cells
Prodrugs / metabolism
Proto-Oncogene Proteins c-bcl-2 / physiology*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Prodrugs; 0/Proto-Oncogene Proteins c-bcl-2; 616-91-1/Acetylcysteine; 70-18-8/Glutathione

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