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Chemical Biological studies for autophagy

Research Project

Project/Area Number 15H03116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
Research InstitutionKeio University

Principal Investigator

IMOTO MASAYA  慶應義塾大学, 理工学部(矢上), 教授 (60213253)

Co-Investigator(Kenkyū-buntansha) 斉木 臣二  順天堂大学, 医学部, 准教授 (00339996)
Co-Investigator(Renkei-kenkyūsha) Tashiro Etsu  慶應義塾大学, 理工学部, 専任講師 (00365446)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywordsオートファジー / パーキンソン / がん / 神経変性疾患
Outline of Final Research Achievements

We constructed GFP-LC3-RFP-expressing cells, and using the cells, we analyzed the diversity and consistency of regulatory signaling in autophagy. The effects of more than 200 small molecular compounds were assessed quantitatively by autophagy regulatory system in cancer cells and neuronal cells. Hierarchical clustering was performed on the subsequent autophagy inhibition profile of the compounds in each cell type. The result was that hierarchical clustering accurately classified the compounds according to their targets. And we distinguished between common and cell type-specific signals responsible for autophagy. SO286, which increased autophagy flux, inhibited the Aggresome formation. SO286 was found to bind SOBP, and by knockdown of SOBP, SO286 failed to inhibit Aggresome formation. This result indicated that SO286 functioned SOBP-dependent manner. We searched for the compounds that induce autophagic cell death, and we isolated Cholest-5-ene-3b,7a-diol from microbial origin.

Report

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

    (25 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results)

  • [Journal Article] Identification of protein kinase C isozymes involved in the anti-proliferative and pro-apoptotic activities of 10-Methyl-aplog-1, a simplified analog of debromoaplysiatoxin, in several cancer cell lines2018

    • Author(s)
      Yusuke Hanaki, Yuki Shikata, Masayuki Kikumori, Natsuki Hotta, Masaya Imoto, Kazuhiro Irie
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 495 Issue: 1 Pages: 438-445

    • DOI

      10.1016/j.bbrc.2017.11.052

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor2017

    • Author(s)
      Y. Shikata Y, T. Yoshimaru, M. Komatsu, H. Katoh, R. Sato, S. Kanagaki, Y. Okazaki, S. Toyokuni, E. Tashiro, S. Ishikawa, T. Katagiri, M. Imoto,
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 4 Pages: 785-794

    • DOI

      10.1111/cas.13175

    • NAID

      120006535004

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells.2017

    • Author(s)
      2.Shikata Y, Kiga M, Futamura Y, Aono H, Inoue H, Kawada M, Osada H, and Imoto M.
    • Journal Title

      Cancer Science

      Volume: 印刷中 Issue: 4 Pages: 772-784

    • DOI

      10.1111/cas.13172

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Antarlides F-H, new members of the antarlide family produced by Streptomyces sp. BB472017

    • Author(s)
      3.Saito S, Fujimaki T, Panbangred W, Sawa R, Igarashi Y, Imoto M.
    • Journal Title

      J. Antiobiotics

      Volume: 印刷中 Issue: 5 Pages: 595-600

    • DOI

      10.1038/ja.2017.6

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Arabilin overcomes resistance to AR-targeted therapy.2017

    • Author(s)
      Fujimaki T, Saito S, Imoto M.
    • Journal Title

      J. Antibiotics

      Volume: 70 Issue: 3 Pages: 328-330

    • DOI

      10.1038/ja.2016.162

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Metacycloprodigiosin induced cell death selectively in b-catenin-mutated tumor cells2017

    • Author(s)
      Ikeda H, Shikata Y, Watanapokasin R, Tashiro E, Imoto M
    • Journal Title

      The Journal of Antibiotics

      Volume: 70 Issue: 1 Pages: 109-112

    • DOI

      10.1038/ja.2016.75

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metacycloprodigiosin (mcPG) induced cell death selectively in β-catenin mutated tumor cells2017

    • Author(s)
      Ikeda H, Shikata Y, Watanapokasin R, Tashiro E, Imoto M.
    • Journal Title

      J. Antibiotics

      Volume: 70 Pages: 109-112

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Synthesis of firefly luciferin analogues and evaluation of the luminescent properties.2016

    • Author(s)
      Ioka S, Saitoh T, Iwano S, Suzuki K, Maki S.A., Miyawaki A, Imoto M, and Nishiyama S.
    • Journal Title

      Chem. Eur. J.

      Volume: 未定

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antarlides: A New Type of Androgen Receptor (AR) Antagonist that Overcomes Resistance to AR-Targeted Therapy2016

    • Author(s)
      Saito S, Fujimaki T, Panbangred W, Igarashi Y, Imoto M.
    • Journal Title

      Angew Chem Int Ed Engl.

      Volume: 55 Issue: 8 Pages: 2718-2732

    • DOI

      10.1002/anie.201510079

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evaluation of drug toxicity profiles based on the phenotypes of ascidian Ciona intestinalis.2015

    • Author(s)
      Mizotani Y, Itoh S, Hotta K, Tashiro E, Oka K, Imoto M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 463 Issue: 4 Pages: 656-60

    • DOI

      10.1016/j.bbrc.2015.05.119

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Mitochondrial uncoupler exerts a synthetic lethal effect against beta-catenin mutant tumor cells2017

    • Author(s)
      井本正哉
    • Organizer
      Asian Chemical Biology Initiative 2017 Ho Chi Minh Meeting
    • Place of Presentation
      Ho Chi Minh (Vietnam)
    • Year and Date
      2017-01-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 謎解きと宝探しの天然物ケミカルバイオロジー2017

    • Author(s)
      井本正哉
    • Organizer
      第52回天然物化学談話会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] シスプラチン持続暴露によるEMT誘導機構の解析2017

    • Author(s)
      田代悦、井本正哉
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Synthetic lethal killing of b-catenin mutant cancer cells by small molecules2017

    • Author(s)
      井本正哉
    • Organizer
      3rd KRIBB-RIKEN Chemical Biology Joint Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Screening of the compounds that modulate cellular bikirubin level in hepatocellular carcinoma HepG2 cells2017

    • Author(s)
      片浦哲志、井本正哉
    • Organizer
      AACR-NCI-EORTC International Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア脱共役剤ノナクチンによるβ-catenin変異がんに対する合成致死誘導2016

    • Author(s)
      四方雄貴、木我真基、田代悦、井本正哉
    • Organizer
      第75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
      2016-10-06
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] MEK阻害剤はベータカテニン変異細胞選択的にアポトーシスを誘導する2016

    • Author(s)
      井本正哉
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ テルサホール(京都府・京都市)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 合成致死を利用したβ-catenin変異がんに対する治療薬シードの探索2016

    • Author(s)
      四方雄貴、木我真基、田代悦、井本正哉
    • Organizer
      第20回日本がん分子標的治療学会学術集会
    • Place of Presentation
      別府国際コンベンションセンター(大分県・別府市)
    • Year and Date
      2016-05-31
    • Related Report
      2016 Annual Research Report
  • [Presentation] β-catenin変異型がん細胞選択的に細胞死を誘導する化合物の探索2016

    • Author(s)
      池田拓慧、田代悦、井本正哉
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌コンベンションセンター(北海道・札幌市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] メラノーマ治療薬として開発されたMEK阻害剤の大腸がん治療薬としての可能性2016

    • Author(s)
      四方雄貴、木我真基、田代悦、井本正哉
    • Organizer
      日本薬学会第136回年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規発光物質の開発を目的としたホタルルシフェリンアナログの合成と活性評価2016

    • Author(s)
      井岡秀二、斉藤毅、岩野智、鈴木孝治、井本正哉、西山繁
    • Organizer
      日本化学会第96回春季年会(2016)
    • Place of Presentation
      同志社大学(京都府・京都市)
    • Year and Date
      2016-03-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification of licopyranocoumarin and glycyrurol from herbal medicines as neuroprotective compounds for parkinson's disease2015

    • Author(s)
      M.Imoto, T.Fujimaki, S.Saiki, E.Tashiro, D.Yamada, N.Hattori
    • Organizer
      PACIFICHEM 2015
    • Place of Presentation
      ホノルル(米国)
    • Year and Date
      2015-12-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] カリウムイオノフォアであるNonactinはβ-catenin変異がん選択的に細胞死を誘導する2015

    • Author(s)
      四方雄貴、田代悦、井本正哉
    • 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
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] β-catenin変異型がん細胞選択的に細胞死を誘導する化合物の探索2015

    • Author(s)
      池田拓慧、四方雄貴、田代悦、井本正哉
    • 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
      2015-10-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 生体内フリーラジカルの検出を目的とした新規ホタルルシフェリンアナログの開発2015

    • Author(s)
      井岡秀二、斉藤毅、岩野智、牧昌次郎、丹羽治樹、井本正哉、西山繁
    • Organizer
      日本ケミカルバイオロジー第10回年会
    • Place of Presentation
      東北大学川内キャンパス(宮城県・仙台市)
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report

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

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