title: The effect of statins on cancer cells--review.
abstract: Statins [3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, abbreviated HMGCR) inhibitors], are well-known cholesterol-depleting agents. Since the early 1990 s, it has been known that statins could be successfully used in cancer therapy, but the exact mechanism(s) of statin activity remains unclear and is now an extensive focus of investigation. So far, it was proven that there are several mechanisms that are activated by statins in cancer cells; some of them are leading to cell death. Statins exert different effects depending on cell line, statin concentration, duration of exposure of cells to statins, and the type of statin being used. It was shown that statins may inhibit the cell cycle by influence on both expression and activity of proteins involved in cell-cycle progression such as cyclins, cyclin-dependent kinases (CDK), and/or inhibitors of CDK. Also, statins may induce apoptosis by both intrinsic and extrinsic pathways. Statin treatment may lead to changes in molecular pathways dependent on the EGF receptor, mainly via inhibition of isoprenoid synthesis. By inhibition of the synthesis of cholesterol, statins may destabilize the cell membrane. Moreover, statins may change the arrangement of transporter OATP1, the localization of HMGCR, and could induce conformational changes in GLUT proteins. In this review, we have tried to gather and compare most of the recent outcomes of the research in this field. We have also attempted to explain why hydrophilic statins are less effective than hydrophobic statins. Finally, we have gathered results from in vivo experiments, presenting the use of statins in combined therapies and discussed a number of molecular targets that could serve as biomarkers predisposing to statin therapy.
authors.affiliation: Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, ul. Joliot-Curie 14a, 50-383, Wrocław, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Matusewicz
authors.forename: Justyna
authors.initials: J
authors.lastname: Meissner
authors.forename: Monika
authors.initials: M
authors.lastname: Toporkiewicz
authors.forename: Aleksander F
authors.initials: AF
authors.lastname: Sikorski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006903:Hydroxymethylglutaryl CoA Reductases; D018844:Cyclin-Dependent Kinases