2022 Fiscal Year Final Research Report
Functional elucidation and basic research for drug discovery of histone modification enzymes involved in early stages of carcinogenesis
| Project/Area Number |
20K07042
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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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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Wakayama Medical University (2021-2022)
Daiichi University, College of Pharmaceutical Sciences (2020) |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ヒストン / メチル化酵素 / 脱アセチル化酵素 / エピジェネティクス |
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| Outline of Final Research Achievements |
Cancer is still the leading cause of death in Japanese. The development and effective use of new anti-cancer drugs are required. In addition to conventional anti-cancer drugs, molecular-targeted drugs that target proteins specifically expressed in cancer cells has been developed. DNA is wrapped around histone proteins, and abnormalities in enzymes that regulate the wrapping of DNA lead to diseases such as cancer. Conversely, inhibitors of those enzymes could be useful as anticancer agents.
In this study, we showed that inhibitors of histone methyltransferases promote the growth inhibition of hepatocellular carcinoma cells when used in combination with multi-kinase inhibitors used in the treatment of liver cancer. We also showed that this effect may involve the promotion of apoptosis.
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| Free Research Field |
生化学・分子生物学、生物系薬学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果により、細胞増殖シグナルを抑制する分子標的薬とヒストン修飾酵素の阻害剤の併用によりがん細胞増殖抑制効果が促進されたことは、分子標的薬の新たな有効な利用方法と考えられる。このことは、既存の薬の有効な利用法の拡大につながる。一方で、促進されない組み合わせもあったことから、有効な組み合わせを見出すためには、個々の阻害剤が細胞内シグナルに与える影響を詳細に解析する必要があることが示された。
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