| Cell line dependence of Bcl-2-induced alteration of glutathione handling. | |
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MedLine Citation:
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PMID: 10656697 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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N F Schor; C M Rudin; A R Hartman; C B Thompson; Y Y Tyurina; V E Kagan |
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Publication Detail:
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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:
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Title: Oncogene Volume: 19 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2000 Jan |
Date Detail:
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Created Date: 2000-02-10 Completed Date: 2000-02-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 472-6 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, University of Pittsburgh, Pennsylvania 15213, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Animals Apoptosis Breast Neoplasms / metabolism Female Glutathione / metabolism* Humans PC12 Cells Prodrugs / metabolism Proto-Oncogene Proteins c-bcl-2 / physiology* Rats Transfection Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA74289/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Prodrugs; 0/Proto-Oncogene Proteins c-bcl-2; 616-91-1/Acetylcysteine; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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