Evaluation of cytotoxic and apoptotic effects of simvastatin in Bone Cancer Cell line (MG-63)

Background & aim: Cancer is a disharmony amongst cell growth and death which results in accumulation of cells. Bone cancer is an absolutely dangerous type of cancer and occurs when the bone-making cells are disrupted. Despite some reports on the anticancer effects of simvastatin, the activity of simvastatin on bone cancer cells has not been reported. The aim of this study was to evaluate the cytotoxic and apoptotic effects of simvastatin on bone cancer MG63 cell line. Methods:In this study, the MG63 cells were cultured and then the cells were incubated with different concentrations of simvastatin for 24 h and the IC50 dose was measured using MTT test. The effects of simvastatin on the mechanisms of cell death such as apoptosis and necrosis were evaluated by flow cytometry. Real-time PCR was used to evaluate the gene expression of caspase 3, 8 and 9 enzymes and Finally, cells treated with IC50 dose of simvastatin were examined by Hoechst staining technique. The collected data were analyzed using the student’s T statistical test and then SPSS software. Results: The MTT results showed that simvastatin at a dose of 155 µg/Ml destroys 50 % of cancer cells. On the other hand, flow cytometry analysis showed that MG63 cells treated with simvastatin (300 µg/Ml) had apoptotic cell death over 90 % compared to the control group. Evaluation of caspase 3, 8 and 9 enzymes using real-time PCR indicated that there was a significant difference in caspase 3 and 9 gene expression (p<0.001) but, no significant difference was observed in caspase 8 gene expression (p<0.05). In the Hoechst staining technique, the discoloration of the treated group cells compared to the control group indicated that the cell nucleus was densified and disintegrated, indicating apoptotic cell death. Conclusion: Finally, the results of this study showed that simvastatin in cell culture medium can induce cytotoxic and apoptotic effects in bone cancer cells (MG63 cell line), therefore, it is important to consider the possibility of using simvastatin in the treatment of bone cancer.