How does fructose affect on carcinogenesis and its progression?

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19640
• 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: Mie University
• Principal Investigator: Murata Mariko 三重大学, 医学系研究科, 教授 (10171141)
• Co-Investigator(Kenkyū-buntansha): 翠川 薫 鈴鹿大学, こども教育学部, 教授 (20393366)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 果糖 / 解糖系 / 発がん / 活性酸素 / 過酸化水素 / GLUT5

Outline of Final Research Achievements

In recent years, consumption of fructose has increased dramatically, and excessive consumption can cause lifestyle-related diseases. In this study, we investigated the involvement of fructose in carcinogenesis. Overexpression of GLUT5, a specific transporter of fructose, was found in human cholangiocarcinoma (CCA). In CCA cancer cells with high GLUT5 expression, cell proliferation and ATP production increased with the addition of fructose, and in a nude mouse subcutaneous implantation model, fructose ingestion promoted tumor growth, and GLUT5 inhibition by siRNA suppressed the tumor growth (Gen Dis, 2022). Fructose significantly produced 8-OHdG in isolated DNA in the presence of copper ions, which was significantly enhanced by the addition of hydrogen peroxide (Mutat Res, 2024). Fructose may contribute to carcinogenesis by the activation of glycolytic system and its ability to generate reactive oxygen species.

Free Research Field

環境衛生学

Academic Significance and Societal Importance of the Research Achievements

果糖消費の激増は、特に高果糖コーンシロップを使用した加工食品による糖質の過剰摂取により、がんを含む生活習慣病のリスクとなる。糖の過剰摂取による糖尿病や肥満が発がんリスクの上昇につながるとの研究がある一方、肥満や糖尿病とは独立して、果糖の摂取量が多い群の大腸癌リスクが増大するという疫学報告がある。我々は、果糖が自動酸化の過程で過酸化水素を生成し、金属イオンとともに酸化還元サイクルを形成することで、酸化的DNA損傷に寄与することを示し、また、GLUT5の過発現ががんの進展に重要であることを明らかにした。本研究は果糖独自の発がんへの関与を示し、学術上意義深い。