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Research on pharmacologically active molecule DIF found in the cellular slime mold Dictyostelium discoieum

Research Project

Project/Area Number 15K07964
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionJuntendo University

Principal Investigator

Kubohara Yuzuru  順天堂大学, スポーツ健康科学研究科, 教授 (00221937)

Co-Investigator(Kenkyū-buntansha) 大島 吉輝  東北大学, 医学系研究科, 特任教授(客員) (00111302)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞性粘菌 / 創薬 / がん / 糖尿病 / ミトコンドリア / 走化性運動 / トリパノソーマ / 抗がん剤 / 転移阻害剤 / 抗菌剤 / DIF / 細胞分化 / 免疫
Outline of Final Research Achievements

DIF-1 is a differentiation-inducing factor and chemotaxis regulator in the cellular slime mold, Dictyostelium discoideum. We have found that DIF-1 and its derivatives possess antitumor activity and glucose-consumption promoting activity, and have advanced development of novel anticancer agents and anti-obesity/anti-diabetic agents using DIF as a seed. In this study, we proceeded with the followings; 1) Analysis of the mechanism underlying the antitumor actions of DIF derivatives, and development of novel anticancer drugs; 2) Analysis of the mechanism underlying the glucose-consumption promoting action of DIF derivatives, and development of novel anti-obesity/anti-diabetic drugs; and 3) analysis of the action mechanisms of DIF-1 in D. discoideum.

Academic Significance and Societal Importance of the Research Achievements

がんや肥満/糖尿病等に起因する生活習慣病は我が国の死亡原因の上位を占めており、これら疾病に対する新規薬剤開発(創薬)に対する社会的ニーズは大きい。しかしながら、新規な創薬資源の探索/開発は容易ではない。我々は土壌微生物の一群である「細胞性粘菌類」を「未利用創薬資源」と位置づけ、粘菌由来の化合物の探索と、それらをシードとした薬剤開発を進めてきた。
とりわけ、本研究では粘菌由来のDIFをシードとしたまったく新しいタイプの抗がん剤と肥満/糖尿病治療薬の開発を進めており、社会的意義は大きいものと考えている。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2019 2017 2016 2015 2014 Other

All Int'l Joint Research (1 results) Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 6 results,  Acknowledgement Compliant: 4 results) Presentation (7 results) (of which Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Toledo(米国)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Dictyostelium: an important source of structural and functional diversity in drug discovery.2019

    • Author(s)
      Kubohara Y, Kikuchi H.
    • Journal Title

      Cells

      Volume: 8 Issue: 1 Pages: 6-6

    • DOI

      10.3390/cells8010006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivatives of <i>Dictyostelium</i> Differentiation-Inducing Factors Inhibit Serum-Dependent Cell Migration of Murine Osteosarcoma LM8 Cells2019

    • Author(s)
      Kubohara Y, Kikuchi H, Oshima Y.
    • Journal Title

      Juntendo Medical Journal

      Volume: 65 Issue: 1 Pages: 71-76

    • DOI

      10.14789/jmj.2019.65.JMJ18-OA10

    • NAID

      130007631916

    • ISSN
      2187-9737, 2188-2126
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Production of Novel Bispyrone Metabolites in the Cellular Slime Mold Dictyostelium giganteum Induced by Zinc(II) Ion2017

    • Author(s)
      Van Hai Nguyen, Haruhisa Kikuchi, Hikaru Sasaki, Kyoichi Iizumi, Yuzuru Kubohara, Yoshiteru Oshima
    • Journal Title

      Tetrahedron

      Volume: 73 Issue: 5 Pages: 583-588

    • DOI

      10.1016/j.tet.2016.12.040

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological Activities of Novel Derivatives of Differentiation-Inducing Factor 3 from <i>Dictyostelium discoideum</i>2017

    • Author(s)
      Takahashi Katsunori、Kikuchi Haruhisa、Nguyen Van Hai、Oshima Yoshiteru、Ishigaki Hirotaka、Nakajima-Shimada Junko、Kubohara Yuzuru
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 11 Pages: 1941-1947

    • DOI

      10.1248/bpb.b17-00484

    • NAID

      130006191965

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthsis, and Biological Activity of Chlorinated Alkylresorcinols from Dictyostelium Cellular Slime Molds2017

    • Author(s)
      Haruhisa Kikuchi, Ikuko Ito, Katsunori Takahashi, Hirotaka Ishigaki, Kyoichi Iizumi, Yuzuru Kubohara, Yoshiteru Oshima
    • Journal Title

      Journal of Natural Products

      Volume: 80 Issue: 10 Pages: 2716-2722

    • DOI

      10.1021/acs.jnatprod.7b00456

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glutathione S-transferase 4 is a putative DIF-binding protein that regulates the size of fruiting bodies in Dictyostelium discoideum.2016

    • Author(s)
      Kuwayama H, Kikuchi H, Oshima Y, & Kubohara Y.
    • Journal Title

      Biochem. Biophys. Rep.

      Volume: 8 Pages: 219-226

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Differentiation-inducing factor 2 modulates chemotaxis via the histidine kinase DhkC-dependent pathway in Dictyostelium discoideum.2016

    • Author(s)
      Kuwayama H, & Kubohara Y.
    • Journal Title

      FEBS Lett.

      Volume: 590 Issue: 6 Pages: 760-768

    • DOI

      10.1002/1873-3468.12111

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid&#8211;stimulated migration of murine osteosarcoma LM8 cells.2015

    • Author(s)
      Kubohara Y, Komachi M, Homma Y, Kikuchi H, & Oshima Y.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 463 Issue: 4 Pages: 800-805

    • DOI

      10.1016/j.bbrc.2015.06.016

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of novel DIF-1 derivatives that selectively suppress innate immune responses.2015

    • Author(s)
      Nguyen VH, Kikuchi H, Kubohara Y, Takahashi K, Katou Y, & Oshima Y.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 23 Issue: 15 Pages: 4311-4315

    • DOI

      10.1016/j.bmc.2015.06.027

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Derivative of Differentiation-Inducing Factor-3 Inhibits PAK1 Activity and Breast Cancer Cell Proliferation.2015

    • Author(s)
      Oladimeji P, Kubohara Y, Kikuchi H, Oshima Y, Rusch C, Skerl R, & Diakonova M.
    • Journal Title

      Int. J. Cancer Clinic. Res.

      Volume: 2 Pages: 3-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Properties of a non-bioactive fluorescent derivative of differentiation-inducing factor-3, an anti-tumor agent found in Dictyostelium discoideum.2014

    • Author(s)
      Kubohara Y, Kikuchi H, Matsuo Y, Oshima Y, & Homma Y.
    • Journal Title

      Biology Open

      Volume: 3 Issue: 4 Pages: 289-296

    • DOI

      10.1242/bio.20146585

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 創薬資源としての細胞性粘菌2017

    • Author(s)
      久保原禅
    • Organizer
      つくば藻類プロティストフォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新規DIF-3誘導体、DIF-3(+3)とHex-DIF-3、の生物活性の検討2017

    • Author(s)
      高橋克典、Nguyen Van Hai、菊地晴久、大島吉輝、嶋田淳子、久保原禅
    • Organizer
      日本細胞性粘菌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] DIF-1とその誘導体が有する抗菌活性の研究2017

    • Author(s)
      久保原禅、佐々木啓、菊地晴久、大島吉輝
    • Organizer
      日本細胞性粘菌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] DIF-1の機能とミトコンドリアの関係2016

    • Author(s)
      久保原禅、菊地晴久、Nguyen Van Hai、桑山秀一、大島吉輝
    • Organizer
      日本細胞性粘菌学会
    • Place of Presentation
      上智大学(東京都千代田区)
    • Related Report
      2016 Research-status Report
  • [Presentation] Jurkat T細胞においてマイトジェン刺激で活性化される転写調節因子のマンガンによる影響2015

    • Author(s)
      中島徹、田中進、田中佑季、秋山珠璃、久保原禅、保坂公平
    • Organizer
      日本生化学会
    • Place of Presentation
      京都国際会議場(京都府京都市)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
  • [Presentation] DIF-2による粘菌走化性運動の制御メカニズム2015

    • Author(s)
      桑山秀一、久保原禅
    • Organizer
      日本細胞性粘菌学会
    • Place of Presentation
      弘前大学(青森県弘前市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 1型糖尿病モデルラットの血糖値に対するDIF-1(経口投与)の効果2015

    • Author(s)
      河原田律子、中村彰男、高橋克典、菊地晴久、大島吉輝、久保原禅
    • Organizer
      日本細胞性粘菌学会
    • Place of Presentation
      弘前大学(青森県弘前市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Remarks] 順天堂大学スポーツ健康科学部健康学科 健康生命科学研究室HP

    • URL

      http://square.umin.ac.jp/jun_health_LS/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Remarks] 順天堂大学スポーツ健康科学部健康学科 健康生命科学 & 環境衛生学 合同HP

    • URL

      http://square.umin.ac.jp/jun_health_LS/index.html

    • Related Report
      2016 Research-status Report
  • [Remarks] 順天堂大学スポーツ健康科学部健康学科 教員・ゼミナール一覧

    • URL

      http://www.juntendo.ac.jp/hss/intro/teacher.html?univ=health

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] マラリア原虫の増殖抑制剤2019

    • Inventor(s)
      美田敏宏、久保原禅、菊地晴久、大島吉輝
    • Industrial Property Rights Holder
      順天堂大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-040682
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2022-03-04  

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