Analysis of the mechanism of anti-cancer effect of 9bw specific on the cells with mutant p53

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24131
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Nihon University
• Principal Investigator: TSUKUNE Naoya 日本大学, 歯学部, 専修医 (20847785)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: ポリエチレングリコール / 口腔がん

Outline of Final Research Achievements

Previously I found that nonaethylene glycol mono (‘4-iodo-4-biphenyl) ester (9BW), a polyethylene glycol derivative synthesized by modifying a compound originally extracted from filamentous bacteria, induced strong growth inhibition in cancer cells carrying mutant type p53, but not in the cells with wild type p53. Since 9bw suppress oxidative phosphorylation of the cells regardless of p53 status, I hypothesized that there are difference between p53 wild-type cells and mutant cells in inhibition rate of ATP production or susceptibility for reduced ATP concentration. To evaluate these hypotheses, I minutely investigated the ATP reduction rate of the cells after 9bw addition, however I could not see clear difference in the reduction rate between p53 wild type and mutant cells. Further analyses are needed to find the reason why 9bw shows stronger cytotoxicity on the cells with mutant p53 than on those with wild type p53.

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9bwが、変異型p53を持つ細胞に対し特に強い毒性を示す原因の解明を試みた。結果的に、現時点で明確な理由はつかめていないが、少なくとも9bw による酸化的リン酸化の抑制とそれに伴うATP産生の低下レベルにはp53野生型と変異型の間で差が無いことが確認できた。多くの抗腫瘍薬は細胞のDNAを損傷し、それにより細胞死を誘導するが、変異型p53を持つ細胞は、こうしたタイプの抗腫瘍薬に対して強い耐性を示すことから、p53変異型の腫瘍細胞に対して特に強い障害性を示す9bwは理想的な抗腫瘍薬候補であり、その作用機序を調べる本研究の社会的意義は大きいと考える。