title: Cytotoxic effect of fluvastatin on MCF-7 cells possibly through a reduction of the mRNA expression levels of SGK1 and CAV1.
abstract: Fluvastatin (FLU) prevents the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid by inhibiting HMG-CoA reductase and decreases cholesterol level. Although the effects of FLU treatment on several cancer types through many mechanisms have been identified, its relationship with unfolded protein response and apoptosis has not been clearly understood. In this recent study, we aimed to investigate the cytotoxic effect of Fluvastatin on MCF-7 cells and define the transcriptional regulation of specific genes during the occurrence of this cytotoxic effect. We administered 0.62, 2.5, 5, and 40 μM FLU on MCF-7 cells singly and in combination with 2-deoxyglucose (2-DG), and we monitored cell viability and proliferation for 48 hours using real-time cell analyzer system (xCELLigence). At the same time, we measured the mRNA expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein, homologous protein (CHOP), caveolin-1 (CAV1), NDRG1 Variant 1 and Variant 2, HMOX1, SGK1, and prostate apoptosis response-4 (PAR4) genes using quantitative real-time polymerase chain reaction (LightCycler 480 II). We accepted GAPDH gene and control groups as the reference gene and calibrator, respectively. We performed relative gene expression analyses of the study groups using the QIAGEN 2009 Relative Expression Software Tool (REST). FLU revealed an antiproliferative and cytotoxic effect on MCF-7 cells, while causing the transcriptional regulation of many genes. Of these genes, the mRNA expressions of CHOP, heme oxygenase 1 (HMOX1), N-myc downstream-regulated gene 1 (NDRG1) V1, and NDRG1 V2 increased. On the other hand, the mRNA expression levels of SGK1 and CAV1 decreased. The antiproliferative effects of FLU may be related to the decreased expression levels of SGK1 and CAV1.
authors.affiliation: Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayis University , Samsun, Turkey .
authors.forename: Osman
authors.initials: O
authors.lastname: Salis
authors.forename: Abdulkerim
authors.initials: A
authors.lastname: Bedir
authors.forename: Sedat
authors.initials: S
authors.lastname: Gulten
authors.forename: Ali
authors.initials: A
authors.lastname: Okuyucu
authors.forename: Canan
authors.initials: C
authors.lastname: Kulcu
authors.forename: Hasan
authors.initials: H
authors.lastname: Alacam
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D007211:Indoles / Q000494:pharmacology*; D061986:MCF-7 Cells; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D051242:Caveolin 1; D000091342:Endoplasmic Reticulum Chaperone BiP; D005229:Fatty Acids, Monounsaturated; D000077340:Fluvastatin; D017874:Immediate-Early Proteins; D007211:Indoles; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099184:Serum-Glucocorticoid Regulated Kinases; C495540:CAV1 protein, human; C000717247:HSPA5 protein, human
keywords: CAV1; MCF-7; SGK1; cytotoxic effect; fluvastatin