Hydrophobic statins induce autophagy in cultured human rhabdomyosarcoma cells.
Statins are widely used to treat hypercholesterolemia, but they are associated with muscle-related adverse events, by as yet, inadequately resolved mechanisms. In this study, we report that statins induced autophagy in cultured human rhabdomyosarcoma A204 cells. Potency differed widely among the statins: cerivastatin induced autophagy at 0.1muM, simvastatin at 10muM but none was induced by pravastatin. Addition of mevalonate, but not cholesterol, blocked induction of autophagy by cerivastatin, suggesting that this induction is dependent on modulation of isoprenoid metabolic pathways. The statin-induced autophagy was not observed in other types of cells, such as human hepatoma HepG2 or embryonic kidney HEK293 cells. Muscle-specific abortive induction of autophagy by hydrophobic statins is a possible mechanism for statin-induced muscle-related side effects.
Araki
Makoto
M
Department of Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Motojima
Kiyoto
K
D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry*; D012208:Rhabdomyosarcoma / Q000473:pathology* / Q000503:physiopathology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors