A new anticancer agent derived from natural fatty acid for the treatment of colon cancer

2016 Fiscal Year Final Research Report

• Project/Area Number: 25430154
• 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, 大学院医学研究科, 教授 (30347158)
• Co-Investigator(Renkei-kenkyūsha): IINUMA Munekazu 岐阜薬科大学, 薬学部, 教授 (70082998) ; FUKAMACHI Katsumi 名古屋市立大学, 大学院医学研究科, 講師 (90381798)
• Research Collaborator: NAGASAWA Hideko 岐阜薬科大学, 薬学部, 教授 ; MORITA Akira (株)日油
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 天然物 / 抗がん薬 / 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 developed a novel anticancer drug, palmitoyl piperidinopiperidine (PPI). In silico simulation exhibited that PPI can bind SH2 domain of STAT3, indicating that this drug blocks dimerization of STAT3, thereby inactivates its function. PPI inhibited transcriptional activity of STAT3, and induced G1 arrest/apoptosis in colon carcinoma cells. There was a marked decrease in expression levels of the Bcl-2, Bcl-xL, and VEGF proteins and an increase in those of the cleaved caspase 3, 7, 8, 9 and PARP proteins. PPI inhibited nuclear translocation of pSTAT3. PPI caused a dose dependent decrease in multiplicity of carcinogen-induced ACF in the rat colon. In a xenograft model, PPI decreased the size and number of blood vessels in the tumor. CAM assays showed a dose-dependent decrease in number of blood vessels. Inhibition of STAT3 by PPI affects the function of molecules related to apoptosis, angiogenesis and cell cycle progression, and contributes to growth inhibition of tumor cells.

Free Research Field

分子毒性学・分子がん治療学