title: Induction of mitotic arrest and apoptosis in human prostate cancer pc-3 cells by evodiamine.
abstract: OBJECTIVE
  Although evodiamine, an alkaloid isolated from Evodiae fructus, has been reported to exert anticancer activities, to our knowledge its target and mechanism of action have not yet been explored. We examined the anticancer activities and action mechanism of evodiamine.
  
  
  METHODS
  Human prostate cancer PC-3 cells were used in this study. The cytotoxic effect and cell growth inhibition were examined using the MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay and sulforhodamine B assay, respectively. The apoptotic effect was determined using TUNEL assay and the progression of cells through the cell cycle and cell apoptosis were examined by FACScan flow cytometry (Becton Dickinson, Sunnyvale, California). In situ mitotic spindle detection and in vitro tubulin polymerization assay were performed by immunofluorescence staining for beta-tubulin and CytoDYNAMIX ScreenTM3 (CDS-03) kits (Cytoskeleton, Denver, Colorado).
  
  
  RESULTS
  It was found that treatment of PC-3 cells with evodiamine decreased the cell number in a concentration and time dependent manner, and effectively inhibited PC-3 cell growth via the induction of cell cycle arrest at the G2/M phase and subsequent apoptosis. In an in situ assay we found that evodiamine inhibited microtubule spindle formation. In a cell-free assay system of tubulin polymerization evodiamine inhibited the polymerization of microtubules in a concentration dependent manner.
  
  
  CONCLUSIONS
  These data suggest that evodiamine shows anticancer activity through inhibition of tubulin polymerization. This antitubulin activity might make evodiamine a potential anticancer drug.
authors.affiliation: Department of Pharmacology, School of Pharmacy and Department of Urology, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Taipei 100, Taiwan, Republic of China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Huang
authors.forename: Jih-Hwa
authors.initials: JH
authors.lastname: Guh
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chueh
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chiang
authors.forename: Che-Ming
authors.initials: CM
authors.lastname: Teng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D008870:Microtubules; D008938:Mitosis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers; D011799:Quinazolines / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D011108:Polymers; D011799:Quinazolines; D014404:Tubulin; C049639:evodiamine