Colon cancer suppression and rescue of healthy cells through Piezo1 inhibition by natural compounds

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Showa University
• Principal Investigator: Yasunori Takayama 昭和大学, 医学部, 講師 (60711033)
• Co-Investigator(Kenkyū-buntansha): 丸山 健太 生理学研究所, 生体機能調節研究領域, 特任准教授 (60724119)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 大腸癌 / フラボノイド / Piezo1

Outline of Final Research Achievements

Piezo1 which is a non-selective cation channel activated by mechanical stimuli on plasma membrane is reportedly involved in colon cancer proliferation. In this project, I found that a natural compound, liquiritigenin, inhibited the Piezo1 currents suppressed the proliferation of colon cancer cells. Therefore, I investigated the proliferation of Piezo1-deficient colon cancer cells. Intriguingly, Piezo1-deficient cancer cells showed more enhancement of the proliferation compared with wild type. This result suggested that there are unknown molecular mechanisms caused by Piezo1 deficit in the cancer exacerbation. Novel therapeutic targets could be identified in future. Additionally, liquiritigenin also induced the cell death in Piezo1-deficient colon cancer cells. This natural compound has the strong possibility as new anti-cancer drugs against more severe cancer cells.

Free Research Field

イオンチャネル

Academic Significance and Societal Importance of the Research Achievements

大腸癌は世界では年間約90万人、本邦では約５万人を死に至らしめる疾患である。また、その死亡者は20歳代から後期高齢者まで生じており、決して特定の年代における問題ではない。その為、大腸癌の細胞生理機能に影響をもたらす化合物の探索や癌増殖抑制手段を発見することは非常に重要である。本研究では、漢方薬の生薬として頻用される甘草に由来するフラボノイドであるリクイリチゲニンが人為的とはいえ増悪化させた大腸癌細胞をも死滅させたことから、将来的には進行癌であったとしても化合物投与により完治できる未来を切り開けるかもしれない。