| Project/Area Number |
17H03992
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Natural medicines
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
荒井 緑 千葉大学, 大学院薬学研究院, 准教授 (40373261)
原 康雅 千葉大学, 大学院薬学研究院, 助教 (10824625)
石川 直樹 千葉大学, 大学院薬学研究院, 助教 (20748826)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | 生理活性 / シグナル伝達 / 生体分子 / 有機化学 / 薬学 |
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| Outline of Final Research Achievements |
Ｉn this study, we examined screening programs using several kinds of luciferase cell-based assays mainly from natural products, with the aim of finding useful low-molecular compounds that act on cell signals that are enhanced in the cancer microenvironment. Screening studies were carried out targeting several intracellular signals involved in stem cell self-renewal and epigenetic gene transcription such as Wnt, Hedgehog, and Notch signals, cancer cell-selective apoptosis-inducing factors, and polycomb-constituting molecules. As a result, a number of useful bioactive natural products having Wnt signal inhibitory activity, TRAIL resistance overcoming activity, Bmi1 promoter inhibitory activity were isolated from our collection of plants and actinomycetes extracts, and their chemical structures were elucidated. We also investigated the mechanism of action of these active compounds through analyzing the effect on the expression of various proteins involved in cancer progression.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で対象とする「がん微小環境」で亢進する細胞シグナルは，正常な幹細胞の自己複製，胚の発生，分化，成人組織再生などにおいて重要な役割を担っていることからきわめて注目度が高く，これまでにも世界的に熾烈な開発競争が繰り広げられてきている．しかしながら，まだ決して十分な状況ではなく，数多くの選択肢を用意することが強く求められている．本研究では「天然物」という独自の素材を用いて，これらのシグナルに作用する数種の低分子化合物が見出された．これらを有効に活用することにより，新しい切り口として創薬研究あるいは各種シグナルを介した生命システムの解明等，周辺分野の研究進展につながることが期待される．
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