Mechanistic elucidation of chemopreventive effects of metformin through analyzing novel identified metformin-binding proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: IIZUMI Yosuke 京都府立医科大学, 医学(系)研究科(研究院), 助教 (20533178)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 結合タンパク質 / がん予防 / ケミカルバイオロジー / ナノ磁性ビーズ / β-catenin / 糖新生抑制タンパク質

Outline of Final Research Achievements

We investigated the chemopreventive effects of the anti-diabetic agent metformin in detail by focusing on our previously identified metformin-binding proteins A and B. The results showed that metformin downregulated β-catenin protein, which is important in the development of colon cancer, by upregulating metformin-binding protein A in colon cancer cells. Metformin was also found to upregulate a gluconeogenesis-suppressive protein, which was reported to be regulated by metformin-binding protein B. However, this upregulation was so small that it was unlikely to contribute to the chemopreventive effects of metformin.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

メトホルミンの標的タンパク質としては、メトホルミンによる糖新生阻害を説明しうる、ミトコンドリアのグリセロリン酸脱水素酵素が報告されていた（Nature, 2014）。本研究により新たに結合タンパク質Aが見出され、結合タンパク質Aを介したメトホルミンによる大腸がんの予防効果の詳細な分子メカニズムが明らかになってきた。結合タンパク質Aとメトホルミンの関係の更なる解析により、メトホルミンによって大腸がんの予防効果が期待できる集団の特定や、結合タンパク質Aを介したより強力ながんの予防法の開発が可能になるかもしれない。