Poteitial new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462618
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: TAKENAGA MITSUKO 聖マリアンナ医科大学, 医学(系)研究科(研究院), 准教授 (10236490)
• Co-Investigator(Kenkyū-buntansha): OHTA YUKI 聖マリアンナ医科大学, 医学部, 助教 (60387066)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: KSP阻害 / キネシンモータータンパク / 細胞周期 / ヒト卵巣がん細胞 / アポトーシス

Outline of Final Research Achievements

Among synthetic kinesin spindle protein (KSP) inhibitor compounds, KPYB10602, a six-member lactam-fused carbazole derivative was the most potent in vitro against cell growth of human ovarian cancer, A2780. KPYB10602 caused dose-dependent suppression of tumor growth in vivo. Mitotic arrest due to KPYB10602 was confirmed in vitro, and was characterized by inhibition of securin degradation. Apoptosis after mitotic arrest was associated with an increase in the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2. Increase of reactive oxygen species (ROS) and caspase pathway were also involved. Furthermore, KPYB10602 caused little neurotoxicity in vivo. Therefore, KPYB10602 could be a promising candidate as an anti-tumor agent with reduced adverse events for treating human ovarian cancer.

Free Research Field

薬理学