title: Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis.
abstract: 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 microg/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(1)cell cycle arrest at lower concentration (25 microg/mL), and triggered G(2)/M arrest and apoptosis at higher concentrations (50 and 100 microg/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.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. ze.tian@childrens.harvard.edu
authors: Ze
authors: Z
authors: Tian
authors: Ruile
authors: R
authors: Pan
authors: Qi
authors: Q
authors: Chang
authors: Jianyong
authors: J
authors: Si
authors: Peigen
authors: P
authors: Xiao
authors: Erxi
authors: E
authors: Wu
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D031885:Cimicifuga / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009368:Neoplasm Transplantation; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000094062:Betulinic Acid
chemical_list: D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D005456:Fluorescent Dyes; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; D016650:Fluorescein-5-isothiocyanate; D000094062:Betulinic Acid