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Type: Artigo de periódico
Title: Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction
Author: Oliveira, KAP
Zecchin, KG
Alberici, LC
Castilho, RF
Vercesi, AE
Abstract: In the present study we analyzed the mechanisms of simvastatin toxicity for the PC3 human prostate cancer cell line. At 10 mu M, 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 mu M, 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.
Subject: Statin
Mitochondrial permeability transition
Intracellular calcium homeostasis
Cell death
Country: EUA
Editor: Springer/plenum Publishers
Citation: Journal Of Bioenergetics And Biomembranes. Springer/plenum Publishers, v. 40, n. 4, n. 307, n. 314, 2008.
Rights: fechado
Identifier DOI: 10.1007/s10863-008-9155-9
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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