A phospholipase c-dependent intracellular Ca2+ release pathway mediates the capsaicin-induced apoptosis in HepG2 human hepatoma cells

The effect of capsaicin on apoptotic cell death was investigated in HepG2 human hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners. Capsaicin induced a rapid and sustained increase in intracellular Ca2+ concentration, and BAPTA, an intracellular Ca2+ chelator, significantly inhibited capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular Ca2+ and apoptosis were not significantly affected by the extracellular Ca2+ chelation with EGTA, whereas blockers of intracellular Ca2+ release (dantrolene) and phospholipase C inhibitors, U-73122 and manoalide. profoundly reduced the capsaicin effects. Interestingly, treatment with the vanilloid receptor antagonist, capsazepine. did not inhibit either the increased capsaicin-induced Ca2+ or apoptosis. Collectively, these results suggest that the capsaicin-induced apoptosis in the HepG2 cells may result from the activation of a "PLC-dependent intracellular Ca2+ release pathway, and it is further suggested that capsaicin my be valuable for the therapeutic intervention of human hepatomas.