Development of a new anticancer agent derived from palmitic acid for the treatment of colon cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K07223
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Nagoya City University
• Principal Investigator: Suzui Masumi 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30347158)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 天然物 / 抗がん物質 / 大腸がん / 転写因子 / STAT3 / 腫瘍選択性 / 構造活性相関 / インシリコ

Outline of Final Research Achievements

We present the first systematic study of the inhibitory effects of palmitoyl piperidinopiperidine, abbreviated as PPI (Japan Patent No. 5597427), on the colon carcinogenesis. Our investigation demonstrate (1) specific cancer cell killing activity, (2) induction of apoptosis of cancer cells, (3) inhibition of angiogenesis, (4) growth inhibition of implanted cancer cells, (5) suppression of the promotion of colon carcinogenesis, (6) inhibition of transcriptional activity of the transcription factor STAT3 by blocking the dimerization of STAT3. These novel effects of PPI provide further evidence that PPI may be a valuable lead compound in the prevention and therapy of colon cancer and possibly other gastrointestinal cancer.

Free Research Field

分子がん治療学、ケミカルバイオロジー、毒性学、天然医薬資源学

Academic Significance and Societal Importance of the Research Achievements

STAT3の阻害薬候補は特異性や毒性の問題により臨床での実用化に至っていない。本研究成果は抗がん物質の化学構造における求核性に着目し、これを誘導体の分子設計に活かすことで特異性を向上させ、毒性の問題を解決することにつなげるという学術的意義がある。いわゆる転写因子抑制薬がもつ弱点を克服し、天然脂肪酸を構造の基本骨格とする新たな創薬カテゴリーの創生につながる社会的にも意義のある研究である。