2022 Fiscal Year Final Research Report
Search for bioactive natural products with overcoming effects on cancer-heterogeneity
| Project/Area Number |
20H03394
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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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| Review Section |
Basic Section 47050:Environmental and natural pharmaceutical resources-related
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高屋 明子 千葉大学, 大学院薬学研究院, 准教授 (80334217)
原 康雅 千葉大学, 大学院薬学研究院, 助教 (10824625)
荒井 緑 慶應義塾大学, 理工学部(矢上), 教授 (40373261)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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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 |
This study is aiming at searching natural products for small-molecular compounds that contribute to "overcoming cancer heterogeneity" by targeting signaling molecules that are enhanced in the cancer microenvironment (niche) that supports the survival and division of cancer stem cells. For this purpose, screening studies were carried out targeting cell signals involved in self-renewal of stem cells and polycomb molecules that regulate epigenetic gene transcription. As a result, various useful active components were isolated from natural product extract collections of plants and actinomycetes, such as Wnt signal inhibitory activity, TRAIL resistance overcoming activity, and Bmi1 promoter inhibitory activity, and chemical structures of active natural products were elucidated. In addition, analysis on their activity mechanisms was examined such as the effects on the expression of various proteins involved in cancer progression.
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| Free Research Field |
天然資源系薬学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，「がん不均一性の克服」に寄与する細胞シグナルをスクリーニング標的としており，注目度が高いため世界的に熾烈な競争が展開されているが，まだ決して十分な状況ではないため，新たな活性化合物の発見が期待されている．本研究では，研究室に保有する植物・放線菌等の天然物エキスという独自の研究対象を用いたスクリーニングを行うことにより，目的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．これらを独自性の高い分子ツールとして有効に活用することにより，細胞シグナルを介した生命現象の解明や，がん不均一性の克服を対象とした創薬研究の一助となるなど，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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