A Novel KSP Inhibitor, KPYB10602, Induces Mitotic Arrest and Cell Death in Breast Cancer Cells

DOI Web Site 参考文献28件 オープンアクセス
  • Kojima-Tsuchiya Seiko
    Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine
  • Ohta Yuki
    Department of Pharmacology, St. Marianna University School of Medicine
  • Takenaga Mitsuko
    Institute of Medical Science, St. Marianna University School of Medicine
  • Niimi Jun
    Institute of Medical Science, St. Marianna University School of Medicine
  • Watanabe Daiki
    Department of Pharmacology, St. Marianna University School of Medicine
  • Tsunoda Satoshi
    Department of Pharmacology, St. Marianna University School of Medicine
  • Ootaki Masanori
    Department of Pharmacology, St. Marianna University School of Medicine
  • Oishi Shinya
    Faculty of Pharmaceutical Sciences, Kyoto University
  • Fujii Nobutaka
    Faculty of Pharmaceutical Sciences, Kyoto University
  • Matsumoto Naoki
    Department of Pharmacology, St. Marianna University School of Medicine
  • Tsugawa Koichiro
    Division of Breast and Endocrine Surgery, Department of Surgery, St. Marianna University School of Medicine

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<p>Purpose: Taxane-based combination chemotherapy remains the predominant treatment for breast cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Kinesin spindle protein (KSP), which is essential for formation of the bipolar mitotic spindle and cell cycle progression through mitosis, has been identified as an attractive target for cancer chemotherapy. We investigated, both in vitro and in vivo, the anti-cancer effect of KPYB10602, a novel KSP inhibitor, in breast cancer.<br/>Materials and Methods: Anti-proliferative activity of KPYB10602 in breast cancer cells was assessed by cell viability assay. The anti-cancer effect and inhibitory mechanism of KPYB10602 in breast cancer cells was further explored by immunofluorescence microscopy, flow cytometry, ELISA, and western blotting. In addition, the anti-tumor effect of KPYB10602 was evaluated in subcutaneous xenograft models.<br/>Results: KPYB10602 showed anti-cancer activity in breast cancer cells. The KPYB10602 treatment was shown to result in induction of mitotic arrest with monopolar spindle formation and then apoptotic cell death. This might occurred via a mitochondria-mediated pathway. KPYB10602 also effectively suppressed tumor growth in a subcutaneous xenograft model.<br/>Conclusion: KSP is a good target for breast cancer chemotherapy, and KPYB10602 has a potential as a novel anti-cancer agent for breast cancer.</p>

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