Journal
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
Volume 40, Issue 4, Pages 307-314Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10863-008-9155-9
Keywords
Statin; Mitochondrial permeability transition; Intracellular calcium homeostasis; Apoptosis; Cell death
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Ask authors/readers for more resources
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 Ca2+ 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available