Screening of cancer cell 3D invasion inhibitors from microbial metabolites

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K01967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Aichi Medical University
• Principal Investigator: Umezawa Kazuo 愛知医科大学, 医学部, 教授 (70114402)
• Co-Investigator(Kenkyū-buntansha): 小出 直樹 愛知医科大学, 医学部, 教授 (50308962)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: がん細胞 / 三次元培養 / 遊走 / 浸潤 / NF-kappa B / I-kappa B kinase / ketomycin / DHMEQ

Outline of Final Research Achievements

In the present research, we have screened low molecular weight compounds that inhibit cancer cell migration from microbial culture filtrates and our own chemical library, then, we have evaluated their effect on three-dimensional (3D) invasion. As a result, we found NF-kappa B inhibitor DHMEQ, migracinal that is a novel derivative of migracin, terfestatin D that is novel microbial metabolite, and a known antibiotic ketomycin as inhibitors of two-dimensional (2D) migration and invasion. Among them, DHMEQ and ketomycin were found to inhibit 3D invasion of cancer cells, and we looked into the mechanism of inhibition. The mechanistic study has shown that ketomycin is a new inhibitor of I-kappa B kinase.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

学術的意義として、新規化合物p-terphenyl glycosideのterfestatin Dとmigracinalを発見し、ketomycinに新規活性を見出した。一方、DHMEQや浸潤を阻害するconophyllineにおいては疾患に関与する多くの新規活性を見出した。社会的意義として、ほとんどの成果を論文および学会発表して知見を社会に広めた。また、海外の大学と多くの共同研究を行って研究のグローバル化を推進させた。さらに3D浸潤は2D浸潤より臨床上の転移に近いモデルとされ、3D浸潤を阻害するDHMEQとketomycinは毒性の少ない抗がん剤として発展する可能性がある。