title: Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells.
abstract: BACKGROUND
  Reversine, a small synthetic purine analogue, has been reported to be effective in tumor suppression. In the present study, we demonstrated an antitumor activity of reversine that could suppress cellular proliferation and induce cell cycle arrest and apoptosis in human breast cancer cell lines.
  
  
  METHODS
  To evaluate whether reversine could suppress cell growth of MCF-7 and MDA-MB-231 cells and induce cell death, the cell viability, cell cycle, and apoptosis were determined in this study.
  
  
  RESULTS
  Reversine treatment in human breast cancer cells reduced cell viability in a dose-dependent manner. Cell cycle accumulation at the G2/M phase in reversine-treated cells was also determined. Moreover, polyploidy was also found in reversine-treated cells. Apoptosis in reversine-treated cells was exhibited with PARP cleavage and caspase-3 and caspase-8 activation, but not caspase-9 activation, indicating that caspase-dependent apoptosis mediated by an extrinsic pathway took place in reversine-treated cells. Furthermore, reversine attenuated cell death in cells pretreated with a pan-caspase inhibitor before reversine treatment.
  
  
  CONCLUSIONS
  In the present study, we demonstrated that reversine contributes to growth inhibition in human breast cancer cells through cell cycle arrest, polyploidy, and/or apoptosis induction. The apoptosis mediated by reversine was induced by the mitochondria-independent pathway. Therefore, the potential role of reversine as a novel therapeutic agent for the treatment of breast cancer is worthy of further investigation.
authors.affiliation: Division of Hematology-Oncology and Blood Bank, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Kuo
authors.forename: Yin-Che
authors.initials: YC
authors.lastname: Lu
authors.forename: Ya-Shin
authors.initials: YS
authors.lastname: Tseng
authors.forename: Chung-Sheng
authors.initials: CS
authors.lastname: Shi
authors.forename: Shu-Hsin
authors.initials: SH
authors.lastname: Chen
authors.forename: Ping-Tzu
authors.initials: PT
authors.lastname: Chen
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Wu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chang
authors.forename: Ying-Ray
authors.initials: YR
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D011123:Polyploidy; D011687:Purines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D011687:Purines; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine