Investigation of the novel cancer treatment drug seeds based on the regulation of heat shock proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20720
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Tokyo University of Science, Yamaguchi
• Principal Investigator: Imahori Daisuke 山陽小野田市立山口東京理科大学, 薬学部, 助教 (10963556)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 天然物化学 / がん予防 / がん細胞毒性 / Hibiscus tiliaceus / Citrus sphaerocarpa

Outline of Final Research Achievements

To investigate the novel cancer treatment drug of natural products derived from plant materials, we isolated 38 compounds, including 8 new compounds. The cell death-inducing activity of isolated compounds alone or combination with Adriamycin (ADR) were observed by time-lapse cell imaging. Although the isolated compounds did not affect the number of mitotic entry cells and dead cells alone, seguinoside K significantly increased the number of dead cells on ADR treated human cervical cancer cells. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human glioblastoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs. In addition, sphaerocarpain I and II showed cytotoxic activity against both U-251 MG and human neuroblastoma cells (SH-SY5Y).

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

抗がん剤感受性増強作用評価を行うことで、化合物単独ではがん細胞の細胞増殖および細胞形態に影響を与えることなく、抗がん剤の感受性増強作用を示すseguinoside Kを見出すことができた。また、抗がん剤抵抗性の原因のひとつとして考えられているがん幹細胞に対して毒性作用を示すvalerianalignans I および IIを見出すことができた。これらの化合物について継続して作用メカニズムの解明を行い、その有用性を明らかにすることで、がん再発予防に貢献できる化合物の開発につながる可能性がある。また、本研究では、今後天然由来医薬シーズの探索を進めるうえで有用な化合物ライブラリーを構築した。