Search for new natural products with anticancer potential in targeting with AMPK, and their combination effects with metformin
| Project/Area Number |
17K08346
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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 |
Natural medicines
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
横須賀 章人 東京薬科大学, 薬学部, 准教授 (20318190)
松尾 侑希子 東京薬科大学, 薬学部, 講師 (70434016)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | AMPK / isoschaftoside / HepG-2 細胞 / 細胞毒性 / メトホルミン / イレイセン / Clematis mandshurica / AMPK活性化 / Glycyrrhiza uralensis / フラボノイド誘導体 / オオキンケイギク / HepG2ヒト肝がん細胞 / 天然物 / フラボノイド配糖体 / 併用効果 / HepG2細胞 / 抗腫瘍活性 / AMPK活性化作用 / 構造決定 / Juniperus horizontalis / ジテルペン類 / 腫瘍細胞毒性 |
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| Outline of Final Research Achievements |
Flavone C-glycosides (1－7) were isolated from Glycyrrhiza uralensis seeds for the first time. Isoschaftoside (3) significantly enhanced the AMPK activity in HepG-2 human hepatoma cells at a sample concentration of 2 mM. On the other hand, apigenin 6,8-di-C-α-L-arabinopyranoside (1) tended to activate AMPK in an inversely dose-dependent manner in HepG-2 cells. As a result of our systematic screening for an increasing cytotoxic effect of metformin by combination of a crude drug extract on HepG-2 cells, the addition of a Clematis Radix extract to metformin was found to enhance the cytotoxicity of metformin against HepG-2 cells. When the AMPK inhibitor was added to the mixture of a Clematis Radix extract and metformin, the combination cytotoxic effect decreased. Phytochemical investigation of the roots and rhizomes of Clematis mandshurica led to the isolation of six triterpene glycosides, including one new compound.
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| Academic Significance and Societal Importance of the Research Achievements |
難治がんの克服を目的とし、天然物を対象とした系統的なAMPK活性化物質の探索研究は、国内外を含め未開拓の研究分野である。本研究課題のように、AMPKに着目した漢方系生薬の活性スクリーニングはこれまでにほとんど例がなく、天然からの新規抗がん剤シーズの探索研究としては新たな試みである。HepG2ヒト肝がん細胞を用いたスクリーニングの結果、イレイセンエキスはメトホルミンの細胞毒性を増強させた。この結果は、AMPK活性化を介した新しいタイプの抗がん剤シーズの発見の端緒となることが期待される研究成果である。
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Report
(5 results)
Research Products
(6 results)
