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Effect of lipid hydroperoxide on cancer progression and its mechanism of action

Research Project

Project/Area Number 20K05934
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionTohoku University

Principal Investigator

Eitsuka Takahiro  東北大学, 農学研究科, 准教授 (30445895)

Co-Investigator(Kenkyū-buntansha) 仲川 清隆  東北大学, 農学研究科, 教授 (80361145)
伊藤 隼哉  東北大学, 農学研究科, 助教 (50781647)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords過酸化脂質 / テロメラーゼ / 癌 / 食品機能性成分
Outline of Research at the Start

癌が進展するためには、癌細胞の発生(発癌)後の増殖過程において劣悪な環境(低酸素、低栄養など)に適応し、様々な悪性形質を獲得することが重要であり、この癌細胞の悪性化こそが、癌が致死的疾病として恐れられている主因である。酸化を受けた脂質(過酸化脂質)による発癌の研究例は複数存在するが、癌の悪性化に与える影響についてはほとんど検証されていない。本研究課題では、過酸化脂質による癌の増悪化の分子機構を解明し、その癌進展を抑制する食品成分を見出すことで、『食による癌抑制』を目指す。本研究は、これらの課題究明を通して超高齢社会に適した食事・医薬を創生することで、健康寿命の延伸に貢献するものである。

Outline of Final Research Achievements

Cellular telomerase activity was increased by lipid hydroperoxide (2-10 μM) in HCT116 human colorectal cancer cells after culturing for 24 hours. As a molecular mechanism, lipid hydroperoxide activated the oncogene c-Myc and telomerase catalytic subunit hTERT via induction of the MAPK pathway, thereby enhancing telomerase activity. Utilizing organoids derived from cancer patients, we investigated the effects of lipid peroxide, and found that activation of telomerase was also observed in colorectal cancer organoids. Simultaneous treatment of HCT116 cells with lipid hydroperoxide and vitamin E (α-tocopherol) inhibited telomerase activation by lipid hydroperoxide.

Academic Significance and Societal Importance of the Research Achievements

過酸化脂質による癌のテロメラーゼ活性化は過去に無い知見であり、抗酸化物質がその作用を抑制することも初めて明らかにしたことから、本研究の独自性・新規性は極めて高い。本研究により得られた成果は食品学、栄養学、生化学にとどまらず、薬学や医学の分野に大きく展開できると考えられ、高齢化が進む日本人の健康維持への貢献 (健康寿命の延伸やQOL(quality of life)の向上)、さらには増大する国民医療費の抑制にもつながるため、社会的意義と波及性が極めて大きい。即ち、本研究成果は、超高齢社会に適した食事・医薬の創生に貢献するものである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Immortalization of common marmoset-derived fibroblasts via expression of cell cycle regulators using the piggyBac transposon2022

    • Author(s)
      Orimoto Ai、Shinohara Haruka、Eitsuka Takahiro、Nakagawa Kiyotaka、Sasaki Erika、Kiyono Tohru、Fukuda Tomokazu
    • Journal Title

      Tissue and Cell

      Volume: 77 Pages: 101848-101848

    • DOI

      10.1016/j.tice.2022.101848

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ethanolamine Plasmalogen Suppresses Apoptosis in Human Intestinal Tract Cells in Vitro by Attenuating Induced Inflammatory Stress2021

    • Author(s)
      Nguma Ephantus、Yamashita Shinji、Kumagai Kei、Otoki Yurika、Yamamoto Ayaka、Eitsuka Takahiro、Nakagawa Kiyotaka、Miyazawa Teruo、Kinoshita Mikio
    • Journal Title

      ACS Omega

      Volume: 6 Issue: 4 Pages: 3140-3148

    • DOI

      10.1021/acsomega.0c05545

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correction: Establishment of immortalized primary cell from the critically endangered Bonin flying fox (Pteropus pselaphon)2020

    • Author(s)
      Tani Tetsuya、Eitsuka Takahiro、Katayama Masafumi、Nagamine Takashi、Nakaya Yumiko、Suzuki Hajime、Kiyono Tohru、Nakagawa Kiyotaka、Inoue-Murayama Miho、Onuma Manabu、Fukuda Tomokazu
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 5 Pages: e0234054-e0234054

    • DOI

      10.1371/journal.pone.0234054

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary and immortalized cell lines derived from the Amami rabbit (Pentalagus furnessi) and evolutionally conserved cell cycle control with CDK4 and Cyclin D1.2020

    • Author(s)
      Orimoto A, Katayama M, Tani T, Ito K, Eitsuka T, Nakagawa K, Inoue-Murayama M, Onuma M, Kiyono T, Fukuda T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 525 Issue: 4 Pages: 1046-1053

    • DOI

      10.1016/j.bbrc.2020.03.036

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] トコトリエノールのがん抑制作用とその高機能化に関する研究2020

    • Author(s)
      永塚貴弘
    • Organizer
      ビタミン学会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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