Pitavastatin induces caspase-mediated apoptotic death through oxidative stress and DNA damage in combined with cisplatin in human cervical cancer cell line

Pitavastatin (PITA) is a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor to treat hypercholesterolemia and in recent studies is focused that its potential anti-cancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells (HeLa) in vitro. Cytotoxicity of PITA (5-200 mu M) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red uptake (NRU) assays for 24, 48, and 72 h. Cell apoptosis and cell cycle analyses were performed in flow cytometry (0.1-100 mu M). The evaluation of genotoxic effects and oxidative DNA damage of PITA (2-200 mu M) were performed with standard comet assay, formamidopyrimidine glycosylase (fpg)-modified comet assay, and reactive oxygen species (ROS) activation in HeLa cells. PITA alone reduced cell viability in a dose-dependent manner (20-200, 20-200, and 5-200 mu M for 24, 48, and 72 h, respectively, in MTT). The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly at 100 mu M for 4 h and 20 mu M for 24 h, respectively. PITA-induced apoptosis, an increased proportion of sub G1 cells, was monitored, and also, it increased the expression of active caspase-9 and caspase-3 and upregulated cleaved poly adenosine diphosphate ribose polymerase (PARP) by western blotting and caspase 3/8/9 multiple assay kit. We conclude that PITA can be used to efficiently cervical cancer studies, and promising findings have been obtained for further studies. Pitavastatin (PITA) has been the focus of recent research due to its potential anticancer effect. This study was aimed to elucidate the effect of PITA alone and in combination with cisplatin on cervical cancer cells in vitro. The combined treatment of PITA with cisplatin resulted in significantly greater inhibition of cell viability. ROS and DNA damage increased significantly. PITA induced apoptosis and increased the expression of active caspase-9 and caspase-3 and upregulated cleaved PARP. In conclusion, PITA can be used for efficient cervical cancer studies.

Automated summary

This study aimed to investigate the effects of Pitavastatin alone and in combination with cisplatin on cervical cancer cells in vitro. The combined treatment of Pitavastatin with cisplatin resulted in significant inhibition of cell viability. Pitavastatin induced apoptosis and increased the expression of active caspase-9 and caspase-3.