Cytotoxicity of Simvastatin in Human Breast Cancer MCF-7 and MDA-MB-231 Cell Lines

Abstract

Objective: Statins, 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors, have been shown to be effective in the treatment of cardiovascular disease. Recent reports demonstrate an anticancer effect induced by statins on lung and prostate cancer cells. The present study aimed to investigate the therapeutic potential of Simvastatin can serve as chemotherapeutic agent against human breast cancer MCF-7 and MDA-MB-231 cell lines. Methods: The cytotoxic effect of simvastatin against breast cancer cells were evaluated using MTT assay. The related mechanism of cell death was further determined by trypan blue staining, morphological changes observation, and drug combination index. Results: The results showed that simvastatin treatment substantially induced cell death in a dose-dependent and time-dependent manner on MCF-7 and MDA-MB-231 cells. Simvastatin exhibited a highly cytotoxic effect on MCF7 and MDA-MB-231 with half-maximal (50%) inhibitory concentration (IC50) 8.9 μM and 4.5 μM respectively. Consistently, we observed antiproliferative effect of Simvastatin was associated with apoptosis on breast cancer cell lines by determination of morphological changes. Moreover, this drug demonstrated a synergistic activity with doxorubicin on triggering cell death in MCF7 cells, but not in MDA-MB-231. Conclusion: Simvastatin has a potent cytotoxic effect resulting in the death of human breast cancer MCF-7 and MDA-MB-231 cell lines, demonstrating its potential as a new candidate for cancer drug.<br />