Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation

Hepatocellular carcinoma is one of the most lethal malignancies and there i s no effective preventive measure in this highly malignant disease to date. In the present study, we investigated the chemopreventive potential of cap saicin (8-methyl-N-vanillyl-6-nonenamide), the principal pungent ingredient found in hot red pepper, in SK-Hep-l hepatocellular carcinoma cells. Treat ment of capsaicin inhibited growth of SK-Hep-l cells in a concentration-dep endent manner while 4-methoxy capsaicin (Met-capsaicin) was less potent. Th is inhibitory effect of capsaicin on SK-Hep-l cell growth was mainly due to the induction of apoptosis as evidenced by DNA fragmentation and nuclear c ondensation. Furthermore, capsaicin prominently reduced the ratio of anti-a poptotic Bcl-2 to pro-apoptotic Bar and consequently increased caspase-3 ac tivity. These results demonstrate that capsaicin efficiently induced apopto sis in SK Hep-l cells through a caspase-3-dependent mechanism, which may co ntribute to its chemopreventive function. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.