Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis.
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.
Tian
Ze
Z
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. ze.tian@childrens.harvard.edu
Pan
Ruile
R
Chang
Qi
Q
Si
Jianyong
J
Xiao
Peigen
P
Wu
Erxi
E
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
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