| Resistance to cisplatin and adriamycin is associated with the inhibition of glutathione efflux in MCF-7-derived cells. | |
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MedLine Citation:
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PMID: 17094488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The impact of the anti-cancer drugs cisplatin (CDDP) and adriamycin (ADR) was investigated on sensitive and resistant MCF-7-derived human breast cancer cells. Cytotoxicity was evaluated by MTT assay, reactive oxygen species (ROS), apoptosis and necrosis by flow cytometry, glutathione (GSH) by HPLC, and Bcl-2, Bax and PARP expression by Western blot. A perturbation of ROS and intracellular GSH levels, and the enhancement of both apoptosis and necrosis were observed in sensitive cells. Transfected MCF-7 cells overexpressing the anti-apoptotic Bcl-2 protein, as well as MCF-7-derived vincristine-resistant cell line (Vcr-R) were resistant to both drugs. This resistance was clearly associated with an unaltered GSH level and with the inhibition of an early GSH efflux. Vcr-R cell resistance seemed to rely on a different mechanism, since it was found to be independent of Bcl-2 expression. Since Bcl-2 overexpression confers the strongest degree of resistance of MCF-7-derived cells, our observations further highlight Bcl-2 as a prime pharmacological target to sensitize cancer cells to chemotherapeutic agents. |
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Authors:
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Sandra Osbild; Laurent Brault; Eric Battaglia; Denyse Bagrel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 26 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 2006 Sep-Oct |
Date Detail:
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Created Date: 2006-11-10 Completed Date: 2006-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 3595-600 Citation Subset: IM |
Affiliation:
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Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UFR SciFA, Université Paul Verlaine-Metz, Campus Bridoux, rue du Général Delestraint, 57070 Metz, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology* Apoptosis / drug effects Blotting, Western Breast Neoplasms / drug therapy, metabolism*, pathology Chromatography, High Pressure Liquid Doxorubicin / pharmacology* Drug Resistance, Multiple Drug Resistance, Neoplasm* Flow Cytometry Glutathione / metabolism* Humans Necrosis Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Reactive Oxygen Species / metabolism Tumor Cells, Cultured Vincristine / pharmacology bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Proto-Oncogene Proteins c-bcl-2; 0/Reactive Oxygen Species; 0/bcl-2-Associated X Protein; 23214-92-8/Doxorubicin; 57-22-7/Vincristine; 70-18-8/Glutathione; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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