Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7.

Abstract

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. This study has been designed to investigation the anticancer effects of simvastatin on breast CSCs. In this study, MCF-7 CSCs were isolated from parent cells and cytotoxic effects of simvastatin were evaluated and compared in both cells. 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. The results were analyzed using one.way ANOVA, followed by Tukey.Kramer posttest. The P < 0.05 was considered as significant. 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. 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.