Search for tubulin regulatory molecules and elucidate the site of active expression for the creation of novel anticancer drugs

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06718
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Nagasaki University
• Principal Investigator: YAMADA Koji 長崎大学, 医歯薬学総合研究科(薬学系), 准教授 (00253469)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: チューブリン分子 / 海洋無脊椎動物 / 海綿動物 / 海草 / AChE阻害活性阻害 / Ｈ５Ｎ1ウイルス増殖抑制 / 抗がん剤 / PC12

Outline of Final Research Achievements

In this study, in order to search for components exhibiting tubulin polymerization / depolymerization inhibitory activity from marine invertebrates and develop the obtained components as seed compounds for new anticancer agents, collection of marine organisms and active constituents was separated. Specifically, each sample animal collected and the microbial culture were processed to prepare a crude extract. As the first screening, we investigated the neurite outgrowth effect on PC12 cells in the presence of nerve growth factor for each crude extract, and showed a neurite outgrowth effect, which may affect tubulin function. Extracts were selected and the active ingredient was isolated. As a result, ceramides, cerebrosides, and cyclic peptides could be isolated from seaweeds, sponges, and marine bacteria and their structures determined.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

がん克服を実現するためには、化学療法で用いられる有効な新規抗がん剤を創出することが不可欠である。そのためには、抗がん剤開発の鍵となるシード化合物の創成が求められる。本研究において、海洋無脊椎動物からシード化合物になりうる活性成分を検索することを目的として実施し、海綿動物、海草、海洋微生物から活性成分を分離することに成功したことは学術的に意義深く、将来医薬開発の糸口になりえる点で社会的意義が大きい。