Poteitial new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor
| Project/Area Number |
25462618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | St. Marianna University School of Medicine |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA YUKI 聖マリアンナ医科大学, 医学部, 助教 (60387066)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / KSP / キネシンモータータンパク質 / 抗がん剤 / ヒト卵巣がん |
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| 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.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor2015
Author(s)
Takenaga, M., Yamamoto, Y., Takeuchi T., Ohta, Y., Tokura, Y., Hamaguchi, A., Asai, D., Nakashima, H., Oishi, S., and Fujii, N.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 463
Issue: 3
Pages: 222-228
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] 新規合成KSP阻害剤のヒト卵巣がんに対する抗腫瘍効果2016
Author(s)
武永美津子, 竹内智起, 山本有貴, 都倉享恵, 新美純, 濱口明美, 太田有紀, 淺井大輔, 大石真也, 中島秀喜, 藤井信孝.
Organizer
日本薬学会第136年会
Place of Presentation
パシフィコ横浜（神奈川県・横浜市）
Year and Date
2016-03-27
Related Report
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[Presentation] 癌細胞に対する新規KSP阻害薬の効果2015
Author(s)
太田有紀, 武永美津子, 大滝正訓, 渡辺実, 武半優子, 飯利太朗, 松本直樹.
Organizer
第36回日本臨床薬理学会
Place of Presentation
京王プラザ（東京都・新宿区）
Year and Date
2015-12-09
Related Report
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