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 may be valuable for the therapeutic intervention of human hepatomas.
Kim
Jung-Ae
JA
College of Pharmacy, Yeungnam University, Kyongsan 712-749, Korea.
Kang
Young Shin
YS
Lee
Yong Soo
YS
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D010738:Type C Phospholipases; D002211:Capsaicin