title: Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells.
abstract: Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.
authors.affiliation: From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555, the Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston, Houston, Texas 77030, maboraha@utmb.edu.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Borahay
authors.affiliation: From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555.
authors.forename: Gokhan S
authors.initials: GS
authors.lastname: Kilic
authors.affiliation: the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, and.
authors.forename: Chandrasekha
authors.initials: C
authors.lastname: Yallampalli
authors.affiliation: From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Snyder
authors.affiliation: From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: the Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia 30912.
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
authors.affiliation: the Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston, Houston, Texas 77030, Darren.F.Boehning@uth.tmc.edu.
authors.forename: Darren
authors.initials: D
authors.lastname: Boehning
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007889:Leiomyoma / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D019821:Simvastatin; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium
keywords: Apoptosis; Calcium; Calcium Channel; Cell Proliferation; Inositol Trisphosphate Receptor (InsP3R); Leiomyoma; Statin; Tumor; Tumor Cell Biology