Document Detail


Resistance to cisplatin and adriamycin is associated with the inhibition of glutathione efflux in MCF-7-derived cells.
MedLine Citation:
PMID:  17094488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sandra Osbild; Laurent Brault; Eric Battaglia; Denyse Bagrel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  26     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2006 Sep-Oct
Date Detail:
Created Date:  2006-11-10     Completed Date:  2006-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3595-600     Citation Subset:  IM    
Affiliation:
Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, UFR SciFA, Université Paul Verlaine-Metz, Campus Bridoux, rue du Général Delestraint, 57070 Metz, France.
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MeSH Terms
Descriptor/Qualifier:
Antibiotics, Antineoplastic / 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:
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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