New Cancer Prevention Strategy; Targeting abnormal cancer suppressor genes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K19692
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MASUDA Mitsuharu 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10305568)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Keywords: 大腸がん / 短縮型APC / がん予防 / 天然物 / スクリーニング

Outline of Final Research Achievements

We evaluated natural products, mainly flavonoids, for their growth inhibitory effects specifically on APC-mutant colon cancer cells in which the WNT pathway is activated. As a result, at 100 microM concentrations, compounds with each of the four predicted patterns were selected: those with no effect on both cell lines, those with equally potent effects on both cell lines, and those with stronger effects on either cell line. However, the specificity of the effects on APC mutant cell lines was not sufficient to separate them from APC normal cells.
It was judged that further screening, such as increasing the number of compounds with different structures, was necessary.

Free Research Field

がん予防

Academic Significance and Societal Importance of the Research Achievements

大腸がん罹患数は増加しており、その革新的な予防法開発は喫緊の課題である。がん抑制遺伝子APCの変異は大腸がんの主要なリスク因子の1つである。近年、典型的な遺伝子変異である短縮型APCに対してのみ特異的に作用し、その増殖を抑制する合成化合物が報告された。しかし、合成品であるため、臨床使用するには、ヒトでの有効性試験や安全性試験など、開発に必要な期間やコストなどが問題となる。
そのため、天然物、食品成分で同様の作用を持つ物質が見つかれば、短期間で、より安全な、がん抑制遺伝子異常を有する大腸がん予防法の確立が期待できる。