Elucidation of protein networks for the mechanism of carcinogenesis through the oxidoreductase in the endoplasmic reticulum

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Hokkaido University
• Principal Investigator: Nomura Takao 北海道大学, 薬学研究院, 特任助教 (90597840)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 癌 / ミトコンドリア / 機能解明

Outline of Final Research Achievements

There are reports that drug-resistant cell lines were created as cancer stem cells other than primary cultured cells in order to obtain cancer stem cells, but these are just "drug-resistant cells" and are true cancer stem cells. Our research team has succeeded in isolating cancer stem cell-like cells, which are present in very small amounts in commercially available cancer cell lines, by combining multiple methods.
The purpose of this study was to investigate the mechanism of a novel HE-I anticancer drug that targets oxidoreductase localized in the endoplasmic reticulum. Under aerobic conditions, no mitochondrial abnormalities were obtained and similar behavior was observed, however, under anaerobic conditions, susceptibility to HE-I was found to increase. This is considered to prove that HE-I is more effective in vivo than in vitro.

Free Research Field

創薬研究

Academic Significance and Societal Importance of the Research Achievements

申請者が開発を続けている抗癌剤は今までの抗癌剤とは標的を別とし、新規作用機序で癌細胞に作用することが考えられる。そのため、既存の癌タンパク質以外で、新たなタンパク質ネットワークが見出されることに期待ができた。以前の研究で見出されたミトコンドリアタンパク質群を本研究では標的としたが、活性酸素種の産生には大きな違いが見出されなかった。しかしながら、嫌気・好気条件ではミトコンドリアによるエネルギー産生には大きな違いがあり、ここに新規抗癌剤の作用機序解明の手がかりが見つかった。