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Analysis of effectiveness of NCL1, a highly selective lysine-specific demethylase 1 inhibitor, for prostate cancer

Research Project

Project/Area Number 26861284
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

ETANI TOSHIKI  名古屋市立大学, 医学(系)研究科(研究院), 研究員 (30600754)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsエピジェネティクス / ヒストン修飾 / LSD1 / 前立腺癌 / オートファジー / LSD1阻害 / 細胞周期停止 / アポトーシス / 動物モデル
Outline of Final Research Achievements

We investigated therapeutic potential of a novel histone lysine demethylase 1 (LSD1) inhibitor, NCL1, in prostate cancer. Prostate cancer cells, LNCaP, PC3 and PCai1 were treated with NCL1, and LSD1 expression and cell viability were assessed. Prostate cancer cells showed strong LSD1 expression, and cell viability was decreased by NCL1. NCL1 also induced G1 cell cycle arrest and apoptosis. In addition, autophagosomes and autolysosomes were induced by NCL1 treatment in LNCaP. Furthermore, LC3-II expression was significantly increased by NCL1 and chloroquine. In mice injected subcutaneously with PCai1 and intraperitoneally with NCL1, tumor volume was reduced with no adverse effects in NCL1-treated mice. Finally, LSD1 expression in human cancer specimens was significantly higher than that in normal prostate glands. NCL1 effectively suppressed prostate cancer growth without adverse events. We suggest that NCL1 is a potential therapeutic agent for hormone-resistant prostate cancer.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect.2015

    • Author(s)
      Etani Toshiki, Suzuki Takayoshi, Naiki Taku, Naiki-Ito Aya, Ando Ryosuke, Iida Keitaro, Kawai Noriyasu, Tozawa Keiichi, Miyata Naoki, Kohri Kenjiro, Takahashi Satoru
    • Journal Title

      Oncotarget

      Volume: 6 Issue: 5 Pages: 2865-2878

    • DOI

      10.18632/oncotarget.3067

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 新規ヒストン脱メチル化酵素阻害剤NCL1の前立腺癌に対する抗腫瘍効果2015

    • Author(s)
      惠谷 俊紀、内木 拓、安藤 亮介、河合 憲康、戸澤 啓一、鈴木 孝禎、郡 健二郎、高橋 智
    • Journal Title

      泌尿器外科

      Volume: 28 Pages: 1289-1292

    • Related Report
      2015 Annual Research Report
  • [Journal Article] NCL1, a highly selective lysine-specific demethylase 1 inhibitor, suppresses prostate cancer without adverse effect.2015

    • Author(s)
      Etani T
    • Journal Title

      Oncotarget

      Volume: 6 Pages: 2865-78

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] NCL1, a selective lysine-specific demethylase1 inhibitor suppresses castration resistant prostate cancer growth2015

    • Author(s)
      Etani Toshiki, Naiki Taku, Iida Keitaro, Ando Ryosuke, Kobayashi Daichi, Kawai Noriyasu, Tozawa Keiichi, Suzuki Takayoshi, Takahasi Satoru, Kohri Kenjiro, Yasui Takahiro
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規ヒストン脱メチル化酵素LSD1の阻害剤NCL1による前立腺癌に対する抗腫瘍効果2015

    • Author(s)
      惠谷 俊紀、内木 拓、飯田 啓太郎、安藤 亮介、河合 憲康、戸澤 啓一、鈴木 孝禎、高橋 智、安井 孝周、郡 健二郎
    • Organizer
      第158回名古屋市立大学医学会例会
    • Place of Presentation
      名古屋市立大学(愛知県名古屋市)
    • Year and Date
      2015-06-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Using the novel selective lysine-specific demethylase 1 inhibitor NCL1 to impair prostate cancer growth.2015

    • Author(s)
      Etani Toshiki, Naiki Taku, Iida Keitaro, Ando Ryosuke, Kobayashi Daichi, Kawai Noriyasu, Tozawa Keiichi, Kohri Kenjiro
    • Organizer
      American Urological Association Annual Meeting 2015
    • Place of Presentation
      New Orleans(USA)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規ヒストン脱メチル化控訴阻害剤NCL1の前立腺癌への治療効果2015

    • Author(s)
      惠谷 俊紀、内木 拓、飯田 啓太郎、小林 大地、安藤 亮介、河合 憲康、戸澤 啓一、林 祐太郎、鈴木 孝禎、郡 健二郎
    • Organizer
      第103回日本泌尿器科学会総会
    • Place of Presentation
      石川県立音楽堂、ANAクラウンプラザホテル金沢 他(石川県金沢市)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規ヒストン脱メチル化酵素阻害剤NCL1の前立腺癌に対する抗腫瘍効果2015

    • Author(s)
      惠谷俊紀
    • Organizer
      第24回泌尿器科分子・細胞研究会
    • Place of Presentation
      JPタワーホール&カンファレンス(東京都・東京)
    • Year and Date
      2015-02-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規ヒストン脱メチル化酵素阻害剤NCL1の前立腺癌に対する抗腫瘍効果2014

    • Author(s)
      惠谷俊紀
    • Organizer
      第31回前立腺シンポジウム
    • Place of Presentation
      東京コンファレンスセンター(東京都・東京)
    • Year and Date
      2014-12-12
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 新規ヒストン脱メチル化酵素阻害剤NCL1の前立腺癌への治療効果2014

    • Author(s)
      惠谷俊紀
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Prostate cancer growth impairment by NCL1, a novel selective lysine-specific demethylase 1 inhibitor.2014

    • Author(s)
      Etani T
    • Organizer
      第109回 American Urological Association Annual Meeting
    • Place of Presentation
      アメリカ合衆国、オーランド
    • Year and Date
      2014-05-18
    • Related Report
      2014 Research-status Report
  • [Presentation] 新規ヒストン脱メチル化酵素阻害剤を用いた前立腺癌治療法の確立に向けた基礎的研究2014

    • Author(s)
      惠谷俊紀
    • Organizer
      第102回日本泌尿器科学会総会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2014-04-24
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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