Study of the COX-independent mechanisms in the efficacy of prevention for colon carcinogenesis by NSAIDs

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19829
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Society medicine, Nursing, and related fields
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TOMOSUGI (HORINAKA) Mano (堀中真野) 京都府立医科大学, 医学(系)研究科(研究院), 講師 (80512037)
• Research Collaborator: AONO yuichi
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: がん予防 / 大腸がん

Outline of Final Research Achievements

Sulindac sulfone is the metabolite of sulindac, a non-steroidal anti-inflammatory drug (NSAID), without anti-inflammatory activity. Sulindac sulfone has been reported to significantly reduce colorectal adenomatous polyps in clinical trials.
In this study, we showed for the first time that sulindac sulfone directly bound to voltage-dependent anion channel (VDAC) 1 and 2. Moreover, we found that sulindac sulfone induced cell cycle arrest and suppresses the mTORC1 pathway by binding and functionally inhibiting VDACs. There is a possibility that the VDAC might be one of the target molecules of sulindac sulfone for pharmacological actions, including chemopreventive effects against colon cancer.

Free Research Field

がん予防医学

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、大腸がん予防効果が期待されているスリンダクスルフォンの新たな作用機序が明らかとなった。スリンダクスルフォンはVDAC1とVDAC2を直接の作用分子とし、大腸がん細胞の増殖を停止させている可能性を初めて示すものである。COX阻害作用を有さないスリンダクスルフォンの作用機序が解明されていくことは、さらに今後の大腸がん化学予防研究の発展に向けた貢献が期待できる。