title: Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7.
abstract: BACKGROUND
  Recent studies have shown the association between statins use and cancer risk reduction. Furthermore the importance of cancer stem cells (CSCs) in tumor initiation, progression and migration has been firmly established in a variety of solid tumors. Hence, the effective targeting of breast CSCs has a potential to improve cancer treatment outcome significantly.
  
  
  OBJECTIVE
  This study has been designed to investigation the anticancer effects of simvastatin on breast CSCs.
  
  
  METHODS
  In this study, MCF-7 CSCs were isolated from parent cells and cytotoxic effects of simvastatin were evaluated and compared in both cells.
  
  
  METHODS
  Stem cell isolation was done by flow cytometry technique and the effects of simvastatin on the stem cell viability, apoptosis and cell cycle were evaluated and compared with parent cells.
  
  
  METHODS
  The results were analyzed using one.way ANOVA, followed by Tukey.Kramer posttest. The P < 0.05 was considered as significant.
  
  
  RESULTS
  Based on the result, simvastatin shows dose-dependent cytotoxic effects on both CSCs and parent MCF-7 cells, whereas the apoptosis induction and the elimination of nonapoptotic programmed death were increased in CSC compared with parent cells. In addition, simvastatin showed the reduction in DNA synthesis and induced cell cycle arrest in the G1 phase in MCF-7 CSCs.
  
  
  CONCLUSIONS
  This finding indicates that simvastatin with specific apoptotic effect on MCF-7 CSC may provide supporting reasons for future in vivo and in vitro statin trials.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Virtual School, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Monireh
authors.initials: M
authors.lastname: Afzali
authors.affiliation: Department of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Melody
authors.initials: M
authors.lastname: Vatankhah
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin