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

• Published in: Journal of ethnopharmacology 2007-11, Vol.114 (2), p.227-233
• Main Authors: Tian, Ze, Pan, Ruile, Chang, Qi, Si, Jianyong, Xiao, Peigen, Wu, Erxi
• Format: Article
• Language: English
• Subjects: Actaea; aerial parts; Animals; Annexin A5 - metabolism; anticarcinogenic activity; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Biological and medical sciences; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell Cycle - drug effects; cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Cimicifuga - chemistry; Cimicifuga foetida; Cimicifuga foetida Linnaeus; cytotoxicity; dose response; Dose-Response Relationship, Drug; EAF; Fluorescein-5-isothiocyanate; Fluorescent Dyes; General pharmacology; H 22 hepatoma; hepatocytes; Hepatocytes - drug effects; hepatoma; Humans; Male; Medical sciences; Mice; Mice, Inbred ICR; Neoplasm Transplantation; neoplasms; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; plant extracts; Plant Extracts - pharmacology; traditional medicine; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2007.08.008

The purpose of this study is to determine whether the ethyl acetate fraction (EAF) from the aerial part of Cimicifuga foetida Linnaeus possesses the anti-tumor action on hepatoma, and therefore, provide evidence for the traditional use of the plant as a detoxification agent. EAF was extracted and its cytotoxicity was evaluated on a panel of Hepatocytes by MTT assay. The IC 50 values of EAF on HepG2, R-HepG2 and primary cultured normal mouse hepatocytes were 21, 43 and 80 μg/mL, respectively. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of EAF. EAF induced G 0/G 1cell 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, activation of downstream effector Caspase 3, and cleavage of poly-ADP-ribose polymerase (PARP) were implicated in EAF-induced apoptosis. In addition, EAF inhibited the growth of the implanted mouse H 22 tumor in a dose-dependent manner with the growth inhibitory rate of 63.32% at 200 mg/kg. In conclusion, EAF may potentially find use as a new therapy for the treatment of hepatoma.