Selective toxicity of Caspian cobra (Naja oxiana) venom on liver cancer cell mitochondria

ABSTRACT

Objective:To explore the cytotoxicity effects of Caspian cobra (Naja oxiana or N.oxiana) venom on hepatocytes and mitochondria obtained from the liver of HCC rats.Methods:In this study,HCC was induced by diethylnitrosamine (DEN),as an initiator,and 2-acetylaminofluorene (2-AAF),as a promoter.Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effect of N.oxiana venom were isolated and mitochondria and cellular parameters related to apoptosis signaling were then determined.Results:Our results showed a raise in mitochondrial reactive oxygen species (ROS)level,swelling in mitochondria,mitochondrial membrane potential (△ψm) collapse and release of cytochrome c after exposure of mitochondria only isolated from the HCC group with the crude venom of the N.oxiana (12.5,25,and 50 μg/mL).This crude venom also induced caspase-3 activation (P ＜ 0.001) in the hepatocytes obtained only from the HCC rat liver.Conclusions:Based on the over all results,we suggested that N.oxiana may be considered as a promising complementary therapeutic agent for the treatment of HCC.