Induction of P3NS1 myeloma cell death and cell cycle arrest by Simvastatin and/or γ-Radiation

Abstract

The present study was conducted to investigate the effect of γ-radiation alone or combined with a cytotoxic drug, simvastatin, on viability and cell cycling of a myeloma cell line. P3NS1 myeloma cells were treated with the selected dose of simvastatin (0.1μM/l) 24 hours prior to γ-irradiation (0.25, 0.5 and 1Gy). The cell viability, induction of apoptosis, cell death, cell cycling, generation of ROS, and expression of P53, Bax, Bcl2, caspase3, PARP1 and Fas genes were estimated. The results indicated that simvastatin (0.1μM/l) treatment for 24 hours prior to γ- irradiation increased cell death to 37.5% as compared to 4.81% by radiation (0.5Gy) alone. It was found that simvastatin treatment before irradiation caused arrest of cells in G0/G1 and G2/M phases as assessed using flow cytometry. Interestingly, simvastatin treatment of P3NS1 cells increased the intracellular ROS production and decreased antioxidant enzyme activity with increased P53, Bax and Caspase3 gene expression while that of Bcl2 was decreased. Consequently, our results indicated that pre-treatment with simvastatin increased radio sensitivity of myeloma tumor cells in addition to apoptotic effects through an intrinsic mitochondrial pathway.