Cimicifuga foetida extract inhibits proliferation of hepatocellular carcinoma via induction of cell cycle arrest and apoptosis

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Purpose: The purpose of this study was to determine whether the acetic acetate fraction(AAF) from the aerial part of Cimicifuga foetida could inhibit the growth of hepatocellular carcinoma cells, and therefore might eventually be useful in the prevention or treatment of Hepatoma.

Methods: AAF was extracted and its cytotoxicity was evaluated on a panel of Hepatocytes by MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of AAF. Implanted mouse H22 hepatoma model was used to demonstrate the tumor growth inhibitory activity of AAF in vivo.

Results: The IC50 values of AAF on HepG2, R-HepG2 and primary cultured normal mouse hepatocytes were 21, 43 and 80 µg/mL, respectively. AAF induced G0/G1cell cycle arrest at lower concentration (25 µg/mL), and triggered G2/M arrest and apoptosis at higher concentrations (50 and 100 µg/mLrespectively). An increase in the ratio of Bax/Bcl-2, activation of downstream effector Caspase 3, and cleavage of poly-ADP-ribose polymerase (PARP) were implicated in AAF-induced apoptosis. In addition, AAF inhibited the growth of the implanted mouse H22 tumor in a dose-dependent manner with the growth inhibitory rate of 63.32% at 200 mg/kg.

Conclusion: AAF may potentially find use as a new therapy for the treatment of hepatoma.