Establishment of new functional food ingredients which are effective for prevention of mesothelioma due to regulation of mesothelioma stem cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K11058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Toyo University
• Principal Investigator: Yano Tomohiro 東洋大学, 食環境科学部, 教授 (50239828)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 中皮腫幹細胞 / Tumorsphere / 薬剤耐性 / 小胞体ストレス / プロテオソーム / オートファジー / トコトリエノール誘導体 / 細胞死

Outline of Final Research Achievements

In order to evaluate if a new preventive strategy for malignant mesothelioma could be established, due to regulation of mesothelioma stem cells, I estimated suppressive effect of T3E, a stable derivative of tocotrienol which was known as a representative ingredient of anti- cancer agent, on mesothelioma stem cells, Firstly, I succeeded in the establishment of a three- dimensional culture system to concentrate on mesothelioma stem cells from parental mesothelioma cells, and subsequently, I investigated whether T3E could act as an effective agent to regulate mesothelioma stem cells. Consequently, I clearly showed that T3E could act as a potential agent to induce cell death in mesothelioma stem cells which have chemo-resistance against conventional anti- mesothelioma agents, based on simultaneous inhibition of proteasome and autophagy.

Free Research Field

癌病態制御学

Academic Significance and Societal Importance of the Research Achievements

アスベスト暴露により発生し、発生数が増加傾向にある難治性が高い中皮腫の新規予防法の開発が急務である。本研究では、中皮腫の根本的な発症要因とされ、中皮腫の難治性の原因とされる中皮腫幹細胞に対して、代表的な食由来の安全性が高いトコトリエノールの安定化誘導体(T3E)が顕著な殺細胞効果を示し、かつ、T3Eが既存の中皮腫治療薬として用いられている抗がん剤に対する中皮腫幹細胞の薬剤耐性を軽減できることを示した。この成果は、将来的に有効な中皮腫予防法の構築につながる重要な成果といえる。