Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells

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• 作者：Chin-Ho Kuo (1)
  Yin-Che Lu (1)
  Ya-Shin Tseng (2)
  Chung-Sheng Shi (3)
  Shu-Hsin Chen (4)
  Ping-Tzu Chen (1)
  Feng-Ling Wu (4)
  Yi-Ping Chang (4)
  Ying-Ray Lee (4) (5)
  
• 关键词：Reversine ; Breast cancer ; Cell cycle ; Polyploidy ; Apoptosis
• 刊名：Breast Cancer
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：21
• 期：3
• 页码：358-369
• 全文大小：
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• 作者单位：Chin-Ho Kuo (1)
  Yin-Che Lu (1)
  Ya-Shin Tseng (2)
  Chung-Sheng Shi (3)
  Shu-Hsin Chen (4)
  Ping-Tzu Chen (1)
  Feng-Ling Wu (4)
  Yi-Ping Chang (4)
  Ying-Ray Lee (4) (5)
  
  1. Division of Hematology-Oncology and Blood Bank, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
  2. Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
  3. Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
  4. Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, No. 539, Jhongsiao Rd., Chiayi, Taiwan
  5. Department of Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan
  
• ISSN：1880-4233

文摘

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.