title: Simvastatin inhibits cancer cell growth by inducing apoptosis correlated             to activation of Bax and down-regulation of BCL-2 gene expression.
abstract: The statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been proven to be effective in lowering cholesterol and as anti-lipid agents against cardiovascular disease. Recent reports demonstrate an anticancer effect induced by the statins through inhibition of cell proliferation. Probably, these effects are due to suppression of the mevalonate pathway leading to the depletion of various downstream products that play an essential role in cell cycle progression, cell signaling and membrane integrity. To date, although many hypotheses have been proposed, the exact mechanism at the basis of cancer cell growth arrest induced by statins is not known. In this study, we have demonstrated that simvastatin, at a dose of 20 µM for 24-72 h, induced in cancer cells but not in normal cells precise features of apoptosis including increased DNA fragmentation while, at the molecular level simvastatin induced overexpression of the pro-apoptotic gene Bax together with an inhibition of BCL-2, the gene that has the well-known function of protecting cells from apoptosis. The simvastatin-mediated induction of apoptosis in similar cancer cells but not in normal cells is very interesting and may be at the basis of cancer therapy using statins, usually in combination with chemotherapy or to be used as a cancer protective drug. Simvastatin may, thus, play a dual prophylactic role as a lipid-lowering drug for the prevention of heart disease and as an anticancer agent to prevent certain types of cancers.
authors.affiliation: Institute of Genetics and Biophysics A. Buzzati Traverso, CNR,                     Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Spampanato
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Maria
authors.forename: Maddalena
authors.initials: M
authors.lastname: Sarnataro
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Giordano
authors.forename: Mario
authors.initials: M
authors.lastname: Zanfardino
authors.forename: Salvatore
authors.initials: S
authors.lastname: Baiano
authors.forename: Maridela
authors.initials: M
authors.lastname: Cartenì
authors.forename: Franco
authors.initials: F
authors.lastname: Morelli
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019821:Simvastatin