Aconiti tuber has been used in oriental herbal medicine since ancient times for analgesic, anti-rheumatic and neurological indications. In the present study, it was investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of A. Tuber (MEBJ) in HepG2 and Hep3B human hepatocarcinoma cells. It was found that MEBJ could inhibit the cell proliferation of HepG2 and Hep3B cells in a concentration-dependent manner, which was associated with induction of apoptotic cell death such as formation of apoptotic bodies and increased populations of apoptotic-sub G1 phase. However, Hep3B cell treated with MEBJ reduced cell viability and induced apoptosis significantly more than in HepG2 cells. Apoptosis of Hep3B cells by MEBJ was connected with an up-regulation of pro-apoptotic Bax expression and a down-regulation of anti-apoptotic Bcl-2 and Bcl-xL in a dose-dependent manner. MEBJ treatment up-regulated the levels of Fas mRNA and protein, and the expression levels of IAPs family members such as cIAP-1 and cIAP-2 were down-regulated by MEBJ treatment. In addition, MEBJ treatment induced the proteolytic activation of caspase-3 and a concomitant degradation of poly (ADP-ribose) polymerase protein. Though further studies will be needed to identify the active compounds and mechanisms that confer the anti-cancer activity of MEBJ, these findings suggest that MEBJ may be a potential chemotherapeutic agent for the control of human cancer cells. (Cancer Prev Res 13, 142-152, 2008)

Keywords: Aconiti tuber, Apoptosis, Bcl-2, Caspase-3