| Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction. | |
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MedLine Citation:
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PMID: 18679777 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present study we analyzed the mechanisms of simvastatin toxicity for the PC3 human prostate cancer cell line. At 10 microM, simvastatin induced principally apoptosis, which was prevented by mevalonic acid but not by cyclosporin A, the inhibitor of calcineurin and mitochondrial permeability transition (MPT). At 60 microM, simvastatin induced the necrosis of PC3 cells insensitive to mevalonic acid. Cell necrosis was preceded by a threefold increase in cytosolic free Ca(2+) concentration and a significant decrease in both respiration rate and mitochondrial membrane potential. Both mitochondrial dysfunction and necrosis were sensitive to the compounds cyclosporin A and bongkrekic acid, as well as the calcineurin inhibitor FK506. We have concluded that simvastatin-induced PC3 cells apoptosis is dependent on 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibition and independent of MPT, whereas necrosis is dependent on mitochondrial dysfunction caused, at least in part, by calcineurin. |
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Authors:
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Kívia A P Oliveira; Karina G Zecchin; Luciane C Alberici; Roger F Castilho; Aníbal E Vercesi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-05 |
Journal Detail:
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Title: Journal of bioenergetics and biomembranes Volume: 40 ISSN: 0145-479X ISO Abbreviation: J. Bioenerg. Biomembr. Publication Date: 2008 Aug |
Date Detail:
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Created Date: 2008-11-17 Completed Date: 2009-02-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7701859 Medline TA: J Bioenerg Biomembr Country: United States |
Other Details:
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Languages: eng Pagination: 307-14 Citation Subset: IM |
Affiliation:
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Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Sao Paulo, Brazil. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Calcineurin / metabolism* Cell Line, Tumor Cell Proliferation / drug effects Humans Male Mitochondria / drug effects, metabolism* Mitochondrial Membrane Transport Proteins / drug effects, metabolism* Prostatic Neoplasms / pathology*, physiopathology* Simvastatin / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Mitochondrial Membrane Transport Proteins; 0/mitochondrial permeability transition pore; 79902-63-9/Simvastatin; EC 3.1.3.16/Calcineurin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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