Theraputic effect of natural flavonoid on bladder cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16705
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Nagoya City University
• Principal Investigator: Iida Keitaro 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (30713945)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膀胱癌 / フラボノイド / 酸化ストレス / mTOR / チオレドキシン

Outline of Final Research Achievements

(1) Luteolin induced apoptosis and a dose-dependent reduction in the number of viable cells; it also increased thioredoxin activity and decreased intracellular ROS production. Luteolin downregulated phospho-S6 and they were canceled by thioredoxin inhibitor, PX-12.
(2) In vivo analysis, no adverse effects were observed by oral intake of luteolin. Immunohistochemistry of tumors showed a decreased Ki67 index, and a reduction of p-S6 expression in the luteolin-treated group. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

本研究において、膀胱癌におけるルテオリンに代表される天然食品由来の抗酸化フラボノイドの効果と安全性を立証できたため、高齢者でも安全に施行できる新たな治療法を提唱することができる。さらには食生活に根ざした食品からの摂取という点で、医療コストを抑制することもでき、予防医学の観点からも有益な研究であると言える。また、既存の薬剤との併用の可否や相乗効果についても今後検討に値すると考えられる。