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Molecular mechanisms for prostate cancer prevention induced by natural flavonoid

Research Project

Project/Area Number 17K11155
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionNagoya City University

Principal Investigator

Naiki Taku  名古屋市立大学, 医薬学総合研究院(医学), 講師 (50551272)

Co-Investigator(Kenkyū-buntansha) 安井 孝周  名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153)
河合 憲康  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (20254279)
安藤 亮介  名古屋市立大学, 医薬学総合研究院(医学), 教授 (30381867)
飯田 啓太郎  名古屋市立大学, 医薬学総合研究院(医学), 臨床研究医 (30713945)
惠谷 俊紀  名古屋市立大学, 医薬学総合研究院(医学), 助教 (30600754)
高橋 智  名古屋市立大学, 医薬学総合研究院(医学), 教授 (60254281)
内木 綾  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (20509236)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords去勢抵抗性前立腺癌 / 天然フラボノイド / ルテオリン / 酸化ストレス / 医療 / 病理学 / 臨床 / トランスレーショナルリサーチ
Outline of Final Research Achievements

Prostate cancer growth is androgen sensitive, therefore, the first-line therapy of prostate cancer is androgen deprivation therapy like castration. However, the therapeutic efficacy is limited and lead to castration resistant prostate cancer (CRPC). Previous study, we established the new CRPC model, and by analyzing them, we newly explored that oxidative stress induced mechanism was highly activated in CRPC. Therefore, in this study, we investigated the therapeutic efficacy of luteolin, which is one of natural flavonoids, in CRPC. As a result, luteolin suppressed CRPC growth both in vitro and in vivo, and the main mechanism of growth suppression was apoptosis regulated by ROS caused by the changes of molecular network. In conclusion, luteolin is promising chemotherapeutic agent for CRPC.

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果から、前立腺発がんや去勢抵抗性の増殖には、GPX2を中心とした酸化ストレス関連遺伝子が重要な働きをしていることが証明され、ルテオリンは経口摂取で前立腺癌の増殖を抑えることが判明した。今後、ルテオリンを主成分とした治療製剤の開発や、日本人が日常で摂取する天然食品を効率よく摂取する方法の開発が可能であれば、新たな治療法の樹立につながると考えられる。さらに今回のルテオリンを用いた酸化ストレス調節法は、他臓器の癌においても応用が可能であることから、新たな発がん・進展抑制につながることも期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Recruitment of miR-8080 by luteolin inhibits androgen receptor splice variant 7 expression in castration-resistant prostate cancer.2019

    • Author(s)
      Naiki-Ito A, Naiki T, Kato H, Iida K, Etani T, Nagayasu Y, Suzuki S, Yamashita Y, Inaguma S, Onishi M, Tanaka Y, Yasui T, Takahashi S.
    • Journal Title

      Carcinogenesis

      Volume: 193 Issue: 8 Pages: 00-00

    • DOI

      10.1093/carcin/bgz193

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses castration-resistant prostate cancer growth via regulation of apoptosis and autophagy.2019

    • Author(s)
      Etani T, Naiki T, Naiki-Ito A, Suzuki T, Iida K, Nozaki S, Kato H, Yagayasu Y, Suzuki S, Kawai N, Yasui T, Takahashi S.
    • Journal Title

      J Clin Med.

      Volume: 8 Issue: 4 Pages: 442-442

    • DOI

      10.3390/jcm8040442

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis.2018

    • Author(s)
      Naiki T, Iida K, Etani T, Nagai T, Tanaka Y, Sugiyama Y, Ando R, Hamamoto S, Banno R, Nagata D, Kawai N, Yasui T.
    • Journal Title

      Cancer Manag Res.

      Volume: 10 Pages: 3669-3677

    • DOI

      10.2147/cmar.s172913

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GPX2 promotes development of bladder cancer with squamous cell differentiation through the control of apoptosis.2018

    • Author(s)
      Naiki T, Naiki-Ito A, Iida K, Etani T, Kato H, Suzuki S, Yamashita Y, Kawai N, Yasui T, Takahashi S.
    • Journal Title

      Oncotarget

      Volume: 22 Issue: 22 Pages: 15847-15859

    • DOI

      10.18632/oncotarget.24627

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early abiraterone acetate treatment is beneficial in Japanese castration-resistant prostate cancer after failure of primary combined androgen blockade.2018

    • Author(s)
      Nagai T, Naiki T (corresponding), Iida K, Etani T, Ando R, Hamamoto S, Sugiyama Y, Akita H, Kubota H, Hashimoto Y, Kawai N, Yasui T.
    • Journal Title

      Prostate Int

      Volume: 1 Issue: 1 Pages: 18-23

    • DOI

      10.1016/j.prnil.2017.07.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metastatic urothelial carcinoma with glandular differentiation that confirmed the response by autopsy specimen to second-line mFOLFOX6 (fluorouracil, oxaliplatin, and leucovorin) plus bevacizumab chemotherapy.2017

    • Author(s)
      Naiki T, Etani T, Naiki-Ito A, Fujii K, Ando R, Iida K, Nagai T, Sugiyama Y, Nakagawa M, Kawai N, Yasui T.
    • Journal Title

      Case Rep Oncol.

      Volume: 3 Issue: 3 Pages: 1057-1064

    • DOI

      10.1159/000484597

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma2017

    • Author(s)
      Naiki T, Iida K, Kawai N, Etani T, Ando R, Nagai T, Tanaka Y, Hamamoto S, Hamakawa T, Akita H, Sugiyama Y, Yasui T.
    • Journal Title

      Journal of Rural Medicine

      Volume: 12 Issue: 2 Pages: 105-111

    • DOI

      10.2185/jrm.2940

    • NAID

      130006233678

    • ISSN
      1880-487X, 1880-4888
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Exploration of new miRNA regulating the androgen receptor splice variant 7 expression in CRPC and application of new clinical strategy.2019

    • Author(s)
      内木拓 内木綾 惠谷俊紀 飯田啓太郎 野崎哲史 永井隆 安藤亮介 河合憲康 高橋智 安井孝周
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Luteolin regulates AR-V7 expression via miRNA recruitment in castration-resistant prostate cancer2019

    • Author(s)
      Naiki T, Naiki-Ito A, Etani T, Iida K, Ando R, Nagai T, Kawai N, Takahashi S, Yasui T.
    • Organizer
      European urological association annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Luteolin has protective role for castration-resistant growth in prostate cancer2018

    • Author(s)
      Naiki T, Naiki-Ito A, Etani T, Nagai T, Iida K, Ando R, Kawai N, Takahashi S, Yasui T.
    • Organizer
      第106回日本泌尿器科学会総会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] エピゲノム変化を介した去勢抵抗性前立腺癌におけるオートファジー制御メカニズムの解明と新規治療法の開発.2017

    • Author(s)
      内木 拓, 惠谷 俊紀, 内木 綾, 飯田 啓太郎, 河合 憲康, 安井 孝周, 高橋 智.
    • Organizer
      第33回前立腺シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] GPX2 is a prognostic marker and has the therapeutic potential through the regulation of oxidative stress in bladder cancer.2017

    • Author(s)
      Naiki T, Naiki-Ito A, Etani T, Iida K, Ando R, Nagai T, Kawai N, Takahashi S, Yasui T.
    • Organizer
      American Urological Association annual meetings
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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