Cytotoxic and Apoptotic Induction Effects of the Venom of Iranian Scorpion ( Odontobuthus bidentatus ) in the Hepatocellular Carcinoma Cell Line (HepG2)

Many efforts are being made to identify new natural substances for the treatment of cancer. Containing enzymes, non-enzymes, ions, and other organic compounds, scorpion venom is a cytotoxic compound that induces apoptosis and necrosis in mammalian cells, and it could be considered as a potential anticancer agent. In this study, the cytotoxicity effects and the ability of apoptosis induction of Odontobuthus bidentatus scorpion venom on HepG2 cells were investigated. Thereafter, the cells were treated with the scorpion venom. Cell cytotoxicity was evaluated using MTT and neutral red tests. By applying catalase activity assay, determination of accumulated NO in cell culture media and GSH levels in the cells, the changes in the cells redox potential was measured and to determine the apoptosis induction, alkaline comet assay, caspase-3, and cytochrome c release assays were exploited. The expression of bax and bcl-2 genes was evaluated using RT-PCR. Considering MTT and neutral red tests, O. bidentatus scorpion venom depicts cytotoxic effects on HepG2 cells. The venom induces apoptosis by increasing NO levels. The catalase enzyme activity and the GSH level were reduced. Also, the activity of caspase-3 and the release of cytochrome c were increased in venom-treated cells. Expression of bax and bcl-2 genes in the treated cells was significantly increased (P < 0.001). These results suggest that O. bidentatus venom is a suitable source of apoptosis-inducing compounds.