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Development of anticancer therapy for urological malignancy using GGCT inhibitors

Research Project

Project/Area Number 15K10584
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionShiga University of Medical Science

Principal Investigator

Kageyama Susumu  滋賀医科大学, 医学部, 講師 (50378452)

Co-Investigator(Kenkyū-buntansha) 富田 圭司  滋賀医科大学, 医学部, 助教 (30640148)
花田 英紀  滋賀医科大学, 医学部, 助教 (40555067)
吉田 哲也  滋賀医科大学, 医学部, 助教 (60510310)
平竹 潤  京都大学, 化学研究所, 教授 (80199075)
吉貴 達寛  滋賀医科大学, 医学部, 准教授 (80230704)
河内 明宏  滋賀医科大学, 医学部, 教授 (90240952)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsγ-グルタミルシクロトランスフェラーゼ / 低分子化合物 / 抗癌剤 / 低分子阻害薬 / 抗がん剤 / 細胞老化
Outline of Final Research Achievements

GGCT (gamma-glutamylcyclotransferase) is known to be one of cancer-promoting proteins. In this study we planned developing the low molecular compounds that can inhibit GGCT function in cancer proliferation. Among the 40 compounds we designed, GA (N-glutaryl-L-alanine) showed the highest GGCT inhibition efficiency. However, since GA had low cell membrane permeability, the diesterified compound, pro-GA, was designed for the purpose of enhancing membrane permeability.
Pro-GA showed a significant inhibition on cell growth in MCF7 breast cancer cell, PC3 prostate cancer cell and HL-60 leukemia cell. Intraperitoneal administration of pro-GA showed a significant tumor growth inhibition in MCF7- and PC3-inoculated mice. Body weight loss and treatment-related death were not observed in these xenograft mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 2015

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] A Novel Prodrug of a γ-Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer.2018

    • Author(s)
      Ii H, Yoshiya T, Nakata S, Taniguchi K, Hidaka K, Tsuda S, Mochizuki M, Nishiuchi Y, Tsuda Y, Ito K, Kageyama S, Yoshiki T.
    • Journal Title

      ChemMedChem.

      Volume: 13 Issue: 2 Pages: 155-163

    • DOI

      10.1002/cmdc.201700660

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prohibitin-2 is a novel regulator of p21WAF1/CIP1 induced by depletion of γ-glutamylcyclotransferase.2018

    • Author(s)
      Taniguchi K, Matsumura K, Kageyama S, Ii H, Ashihara E, Chano T, Kawauchi A, Yoshiki T, Nakata S.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 496 Issue: 1 Pages: 218-224

    • DOI

      10.1016/j.bbrc.2018.01.029

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Depletion of gamma-glutamylcyclotransferase induces autophagy prior to cellular senescence in cancer cells2018

    • Author(s)
      Keiko Taniguchi, Kengo Matsumura, Susumu Nakata*, Hiromi ii, Susumu Kageyama, Akihiro Kawauchi, Tatsuhiro Yoshiki
    • Journal Title

      American Journal of Cancer Research

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design of fluorogenic probes and fluorescent-tagged inhibitors for γ-glutamyl cyclotransferase2017

    • Author(s)
      Yoshiya T, Ii H, Tsuda S, Mochizuki M, Kageyama S, Yoshiki T
    • Journal Title

      J Pept Sci

      Volume: 印刷中 Issue: 7-8 Pages: 618-623

    • DOI

      10.1002/psc.2984

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis and GGCT Inhibitory Activity of <i>N</i>-Glutaryl-L-alanine Analogues2016

    • Author(s)
      Ii H, Yoshiki T, Hoshiya N, Uenishi J
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 64 Issue: 7 Pages: 785-792

    • DOI

      10.1248/cpb.c16-00167

    • NAID

      130005160076

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Depletion of γ-glutamylcyclotransferase inhibits breast cancer cell growth via cellular senescence induction mediated by CDK inhibitor upregulation2016

    • Author(s)
      Matsumura K, Nakata S, Taniguchi K, Ii H, Ashihara E, Kageyama S, Kawauchi A, Yoshiki T
    • Journal Title

      BMC Cancer

      Volume: 16 Pages: 748-748

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] γ-グルタミルシクロトランスフェラーゼ阻害剤の細胞老化を介した細胞増殖抑制効果と抗がん剤併用によるその効果の増強2018

    • Author(s)
      高木寛子,飯居宏美,中田 晋,谷口恵香,吉矢 拓,津田修吾,望月雅允,影山 進,吉貴達寛
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規γ-グルタミルシクロトランスフェラーゼ阻害剤の抗腫瘍効果の検討2018

    • Author(s)
      飯居宏美,中田 晋,谷口恵香,吉矢 拓,津田修吾,望月雅允,影山 進,吉貴達寛
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 担癌マウスにおけるγ-グルタミルシクロトランスフェラーゼ阻害剤の抗腫瘍効果2017

    • Author(s)
      飯居宏美,中田 晋,谷口恵香,影山 進,吉貴達寛
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] γ-グルタミルシクロトランスフェラーゼ(GGCT)の発現低下はオートファジーを介して細胞老化を誘導する2017

    • Author(s)
      谷口恵香,中田 晋,松村健吾,飯居宏美,影山 進,河内明宏,吉貴達寛
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規癌増殖因子GGCT/C7orf24を標的とした抗がん剤の開発 -小規模プロテオーム解析からの挑戦-2017

    • Author(s)
      影山 進,花田英紀,窪田成寿,富田圭司,村井亮介,小林憲市,飯居宏美,中田 晋, 吉矢 拓,礒野高敬,湯浅 健,吉貴達寛,河内明宏
    • Organizer
      第105回日本泌尿器科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Depletion of γ-glutamylcyclotransferase inhibits cancer cell growth through cellular senescence induction2016

    • Author(s)
      Kengo Matsumura, Susumu Nakata, Keiko Taniguchi, Hiromi Ii, Eishi Ashihara, Susumu Kageyama, Akihiro Kawauchi, Tatsuhiro Yoshiki
    • Organizer
      2016 ASCB (American Society of Cell Biology) Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] CDKI誘導を介したγ-グルタミルシクロトランスフェラーゼの抑制による細胞老化誘導2016

    • Author(s)
      松村健吾,中田 晋,飯居宏美,芦原英司,影山 進,河内明宏,吉貴達寛
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Depletion of γ-glutamylcyclotransferase inhibits cancer cell growth via celluar snescence caused by CDK inhibitor induction2016

    • Author(s)
      Kengo Matsumura, Susumu Nakata, Hiromi Ii, Eishi Ashihara, Susumu Kageyama, Akihiro Kawauchi, Tatsuhiro Yoshiki
    • Organizer
      24th Biennial Congress of the European Association for Cancer Research
    • Place of Presentation
      Manchester, UK
    • Year and Date
      2016-07-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] γ-グルタミルシクロトランスフェラーゼ (GGCT) 基質 "LISA-101" の開発と応用2015

    • Author(s)
      吉矢 拓、飯居 宏美、津田 修吾、影山 進、吉貴 達寛、西内 祐二
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
    • Place of Presentation
      神戸市
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] γ-グルタミルシクロトランスフェラーゼ:蛍光基質 LISA-101の開発とインヒビター探索2015

    • Author(s)
      吉矢 拓、飯居 宏美、津田 修吾、影山 進、吉貴 達寛、西内 祐二
    • Organizer
      第20回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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