Simvastatin induced actin cytoskeleton disassembly in normal and transformed fibroblasts without affecting lipid raft integrity

• Published in: Cell biology international 2017-09, Vol.41 (9), p.1020-1029
• Main Authors: Chubinskiy‐Nadezhdin, Vladislav I., Negulyaev, Yuri A., Morachevskaya, Elena A.
• Format: Article
• Language: English
• Subjects: Actin; actin cytoskeleton; Actin Cytoskeleton - drug effects; Actin Cytoskeleton - metabolism; Actins - metabolism; Animals; Antitumor agents; Apoptosis; BALB 3T3 Cells; Cell Line; Cell lines; Cell Membrane - metabolism; Cell Survival - drug effects; Cholesterol; Cholesterol - metabolism; Cytoskeleton; Dismantling; Dose-Response Relationship, Drug; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hypercholesterolemia; Lipid rafts; Lipids; Low density lipoprotein; Mammalian cells; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Mice; Simian virus 40; Simvastatin; Simvastatin - pharmacology; Staining; Statins; Transfection; Transformed cells; transformed fibroblasts
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.10812

Statins are the most commonly prescribed agents used to modulate cholesterol levels in course of hypercholesterolemia treatment because of their relative tolerability and LDL‐C lowering effect. Recently, there are emerging interests in the perspectives of statin drugs as anticancer agents based on preclinical evidence of their antiproliferative, proapoptotic, and anti‐invasive properties. Functional impact of statin application on transformed cells still remains obscure that requires systematic study on adequate cellular models to provide correct comparison with their non‐transformed counterparts. Cholesterol is the major lipid component of mammalian cells and it plays a crucial role in organization, lateral heterogeneity, and dynamics of plasma membrane as well as in membrane‐cytoskeleton interrelations. To date, it is uncertain whether cellular effects of statins involve lipid‐dependent alteration of plasma membrane. Here, the effects of simvastatin on lipid rafts, F‐actin network and cellular viability were determined in comparative experiments on transformed fibroblasts and their non‐transformed counterpart. GM1 lipid raft marker staining indicated no change of lipid raft integrity after short‐ or long‐term simvastatin treatments. In the same time, simvastatin induced cytoskeleton rearrangement including partial F‐actin disruption in cholesterol‐ and lipid raft‐independent manner. Simvastatin dose‐dependently affected viability of BALB/3T3 and 3T3B‐SV40 cell lines: transformed fibroblasts were noticeably more sensitive to simvastatin comparing to non‐transformed cells.