Induction of apoptosis by capsaicin in hepatocellular cancer cell line SMMC-7721 is mediated through ROS generation and activation of JNK and p38 MAPK pathways

Capsaicin, one of the major pungent ingredients found in red peppers, has been shown to have anti-carcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human hepatocellular cancer cell line SMMC-7721, as well as the possible mechanisms involved. Treatment of SMMC-7721 cells with capsaicin resulted in a dose-dependent inhibition of cell-viability and induction of apoptosis which was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. These effects were significantly blocked when cells were pretreated with a general antioxidant N-acetyl cysteine (NAC). We also found that capsaicin induced JNK and p38 MAPK phosphorylation. JNK and p38 MAPK inhibitor effectively blocked capsaicin-induced SMMC-7721 cell apoptosis. In addition, NAC completely blocked phosphorylation of JNK and p38 MAPK induced by capsaicin. Our results indicate that capsaicin induced in SMMC-7721 cell apoptosis through generation of intracellular ROS and activation of JNK and p38 MAPK pathways.