Naja sumatrana venom cytotoxin, sumaCTX exhibits concentration-dependent cytotoxicity via caspase-activated mitochondrial-mediated apoptosis without transitioning to necrosis

The mechanism of suma-cytotoxin (sumaCTX)-induced cytotoxicity is poorly understood, especially in the transition of cell death pattern. This study examines its cytotoxicity, caspase-3/7 activity, mitochondrial functions, and occurrence of apoptosis. The sumaCTX triggered cytotoxicity in MCF-7 cells before 24 h, with activation of caspase-3/7 and mitochondrial depolarization, followed by a substantial percentage of AV⁺ apoptotic cells. The absence of HMGB1 suggested apoptosis was the profound cell death independent of its membrane perturbing effect, without transitioning into necrosis. Its cytotoxicity was a concentration-dependent but not time-dependent process. The findings provide valuable insight into mechanisms of sumaCTX-induced cytotoxicity in breast cancer cells.