Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

BACKGROUND: Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma. METHODS: The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H(22 )hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA in vivo. RESULTS: The IC(50 )values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G(0)/G(1 )cell cycle arrest at lower concentration (25 μg/ml), and triggered G(2)/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H(22 )tumor in a dose-dependent manner. CONCLUSION: TGA may potentially find use as a new therapy for the treatment of hepatoma.