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Mechanism of (S)-erypoegin K having tumor cell-specific cytotoxicity

Research Project

Project/Area Number 16K08311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Natural medicines
Research InstitutionMeijo University

Principal Investigator

Kaneda Norio  名城大学, 薬学部, 教授 (00144139)

Co-Investigator(Kenkyū-buntansha) 村田 富保  名城大学, 薬学部, 准教授 (80285189)
Research Collaborator Hikita Kiyomi  
Imanishi Susumu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords抗腫瘍活性物質 / イソフラボン / ヒト白血病 / 抗腫瘍活性 / アポトーシス / 白血病細胞株 / 標的タンパク質 / 光親和性小分子固定化法 / リンパ腫細胞株 / グリオキサラーゼI / メチルグリオキサール / 薬学 / 天然物化学 / グリオキサラーゼ I / エリポエギンK
Outline of Final Research Achievements

We isolated an isoflavone from stem bark of Erythrina poeppigiana which is effective against human leukemia and gastric cancer cells. The isoflavone named as erypoegin K shows cancer-specific activity because it showed very weak toxicity toward human normal lymphocytes. Erypoegin K also showed anti-tumor activity, when administered intraperitonealy, against the tumor-bearing mouse with a xenograft of human gastric cancer cells. The growth inhibitory effect on tumor cells was comparable or stronger than that of 5-fluorofracil, one of the typical anti-tumor agents. We found that erypoegin K can inhibit the enzyme activity which is involved in cell division in the cell cycle. It was suggested that erypoegin K may be a useful and effective lead compound for the development of new anti-tumor drugs.

Academic Significance and Societal Importance of the Research Achievements

現在、日本人の死因の3分の1はがんであることから、新しい抗がん剤の開発は社会的に重要な課題である。我々は植物に含まれる抗がん活性を有する化合物の中から、(S)-エリポエギンKというイソフラボン化合物を発見した。本化合物はヒト白血病や胃がん細胞に対して有効で、その作用機構は細胞の分裂に関与する酵素の阻害であることが示唆された。本研究は新規の抗がん剤を開発するための基本化合物となる可能性がある。

Report

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

    (10 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Structural analysis of the inhibitory effects of polyphenols, (+)‐hopeaphenol and (-)‐isohopeaphenol, on human SIRT12018

    • Author(s)
      Loisruangsin Arthorn、Hikita Kiyomi、Seto Norikazu、Niwa Masatake、Takaya Yoshiaki、Kaneda Norio
    • Journal Title

      BioFactors

      Volume: 45 Issue: 2 Pages: 253-258

    • DOI

      10.1002/biof.1479

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effect of resveratrol dimers and tetramers isolated from Vitaceous and Dipterocarpaceous plants on human SIRT1 enzyme activity2018

    • Author(s)
      Hikita Kiyomi、Seto Norikazu、Takahashi Yusuke、Nishigaki Ayako、Suzuki Yuya、Murata Tomiyasu、Loisruangsin Arthorn、Aminah Nanik Siti、Takaya Yoshiaki、Niwa Masatake、Kaneda Norio
    • Journal Title

      Natural Product Communications

      Volume: 13 Pages: 1531-1534

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Potent apoptosis-inducing activity of erypoegin K, an isoflavone isolated from Erythrina poeppigiana, against human leukemia HL-60 cells2018

    • Author(s)
      Hikita Kiyomi、Hattori Natsuki、Takeda Aya、Yamakage Yuko、Shibata Rina、Yamada Saori、Kato Kuniki、Murata Tomiyasu、Tanaka Hitoshi、Kaneda Norio
    • Journal Title

      Journal of Natural Medicines

      Volume: 72 Issue: 1 Pages: 260-266

    • DOI

      10.1007/s11418-017-1147-9

    • NAID

      40021638339

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] イソフラボン(S)-erypoegin Kによるヒト白血病細胞株HL-60に対するアポトーシス誘導機序の解明2019

    • Author(s)
      疋田清美、纐纈 愛、溝口 葵、松岡健太、三枝聡実、村田富保、浅尾直樹、田中 斎、金田典雄
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] (S)-erypoegin Kによるヒト白血病細胞株HL-60に対するアポトーシス誘導活性2018

    • Author(s)
      鈴木千晴、纐纈 愛、杉山実咲季、疋田清美、村田富保、浅尾直樹、加藤國基、田中 斎、金田典雄
    • Organizer
      第64 回日本薬学会東海支部大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 植物由来レスベラトロールオリゴマーの白血病細胞株HL-60の細胞増殖に対する効果2018

    • Author(s)
      佐藤公亮、疋田清美、岡部有里、村田富保、高谷芳明、丹羽正武、金田典雄
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Biological study on the phytochemical compounds with anti-inflammatory and apoptosis-inducing activities2018

    • Author(s)
      Norio Kaneda
    • Organizer
      第8回南京・名古屋・瀋陽薬学シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Apoptosis-inducing activity of resveratrol oligomers from plants against human leukemia HL-60 cells2018

    • Author(s)
      Aoi Mizoguchi, Kenta Matsuoka, Kiyomi Hikita, Tomiyasu Murata, Yoshiaki Takaya, Masatake Niwa, Norio Kaneda
    • Organizer
      第8回南京・名古屋・瀋陽薬学シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト急性前骨髄球性白血病細胞株HL-60におけるDoxorubicinまたはCytarabineと(S)-Erypoegin Kの併用効果2017

    • Author(s)
      外山葵、疋田清美、村田富保、浅尾直樹、加藤國基、田中齊、金田典雄
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台市
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] (S)-erypoegin KのHL-60細胞に対するアポトーシス誘導活性2017

    • Author(s)
      疋田清美、杉山実咲季、村田富保、浅尾直樹、加藤國基、田中 斎、金田典雄
    • Organizer
      2017年度生命科学系学会合同年次大会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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