2020 Fiscal Year Final Research Report

Analysis of the mechanism of tumor specific growth inhibition by polyethylene glycol derivative PEG-X

Research Project

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Project/Area Number	18K07275
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	Nihon University
Principal Investigator	FUJIWARA Kyoko 日本大学, 歯学部, 准教授 (40595708)
Co-Investigator(Kenkyū-buntansha)	尾崎俊文千葉県がんセンター(研究所), 発がん研究グループ DNA損傷シグナル研究室, 室長 (40260252)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	ポリエチレングリコール / 増殖抑制効果
Outline of Final Research Achievements	Nonaethylene glycol mono (‘4-iodo-4-biphenyl) ester (PEG-X) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria. Although PEG-X shows remarkable inhibition of tumor cell growth, it has limited effect on normal fibroblast. In the present study, we examined the efficacy of PEG-X on tumor cells and fibroblast, and investigated the molecular mechanisms underlying the exclusive cytotoxic effects of PEG-X on tumor cells. Our results indicated that PEG-X induced cell death in tumor cells by decreasing the production of ATP. Metabolome analysis and measurement of oxygen consumption indicated that PEG-X markedly suppressed oxidative phosphorylation (OXPHOS). Further analyses indicated that PEG-X inhibited the activity of mitochondrial respiratory complex I. Based on the results of the present study, PEG-X is a good candidate as a novel anti-cancer agent.
Free Research Field	腫瘍学
Academic Significance and Societal Importance of the Research Achievements	本研究では新規ポリエチレングリコール誘導体PEG-Xが、ミトコンドリアの呼吸鎖複合体Iの機能を阻害することにより細胞の増殖抑制を行うことを明らかとした。PEG-Xは腫瘍細胞特異的に細胞障害性を持つことから、副作用の少ない抗腫瘍薬として非常に有望な分子である。PEG-Xの正確な作用機序を解明したことにより、新規の実用可能な抗腫瘍薬の開発に一歩近づいた点に、本研究の社会的意義があると考える。PEG-Xによる酸化的リン酸化の抑制は正常細胞においても腫瘍細胞においても同等にみられたことから、PEG-Xの効果がなぜ腫瘍特異的であるのか、今後さらなる解析により検討を進めていきたい。