Detection of bioactive substances from marine organisms targeting for candidates of driver mutation gene in oral cancer and applying them to drug design study

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11838
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: YOSHIOKA Yukio 広島大学, 医系科学研究科(歯), 助教 (20335665)
• Co-Investigator(Kenkyū-buntansha): 岡本 哲治 広島大学, 医系科学研究科(歯), 教授 (00169153) ; 小鹿 一 名古屋大学, 生命農学研究科, 教授 (50152492) ; 山崎 佐知子 広島大学, 病院(歯), 病院助教 (00632001)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 海洋生物 / 口腔癌 / 扁平上皮癌 / ドライバー遺伝子 / 創薬 / 抗癌剤 / 毒性試験 / Crambescidin

Outline of Final Research Achievements

We analyzed antitumor effect of bioactive substances purified from red seaweed (Laurencia intricate) and sponge (Clathria bulbotoxa) living at ocean near Indochina sea. We purified the bioactive substances on the basis of anti-proliferative activity at squamous cell carcinoma on serum free medium and identified the strongest bioactive substances by LC/MS. All of bioactive substances isolated from red seaweed were brominated sesquiterpene, which had been well known before. 6 kinds of bioactive substances from sponge were all Crambescidin. Crambescidin657 had the strongest antitumor effect for squamous cell carcinoma cells and its half maximal inhibitory concentration for A431 cell was 50nM. We extracted RNA from A431 cell treated with 50nM Crambescidin657 for 24hours on serum free medium. Exhaustive gene analysis using by DNA microarray indicated the downregulation of cell cycle related genes and upregulation of cholesterol synthesis enzyme, inflammation related genes.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

ドライバー遺伝子は，がんの発生・進展において直接，重要な役割を果たす癌遺伝子，癌抑制遺伝子であり，現在これらの変異を標的とした治療薬の開発がめざましい．口腔癌をはじめとした頭頸部癌においては，ドライバー遺伝子が同定されていないため，他がん種と比較して分子標的治療薬の開発とその臨床応用はかなり遅れている． 口腔癌のドライバー遺伝子候補とその変異を同定し，それを標的とした分子標的治療薬を開発することは口腔癌治療戦略の上でかなり重要である．特に海洋生物由来の生理活性物質から新規抗癌剤創薬の過程でドライバー遺伝子候補を同定することは画期的である．