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Search and functional analysis of natural products targeting intracellular signals that control the development and recurrence of cancer

Research Project

Project/Area Number 26293022
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Natural medicines
Research InstitutionChiba University

Principal Investigator

Ishibashi Masami  千葉大学, 大学院薬学研究院, 教授 (90212927)

Co-Investigator(Kenkyū-buntansha) 荒井 緑  千葉大学, 薬学研究科(研究院), 准教授 (40373261)
石川 直樹  千葉大学, 薬学研究科(研究院), 助教 (20748826)
當銘 一文  富山大学, 和漢医薬学総合研究所, 准教授 (80563981)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords生理活性 / シグナル伝達 / 有機化学 / 薬学 / 生体分子 / 癌
Outline of Final Research Achievements

This study aims to find useful low-molecular compounds by screening natural products having effects on intracellular signals that control the development and recurrence of cancer. In particular, screening studies were carried out targeting several intracellular signals that have essential roles of treatment-resistance of cancer cells and acquiring pluripotency of stem cells. As a result, we have isolated many useful active compounds that have inhibitory effects on Wnt and Hedgehog signal pathways, and also obtained natural products having TRAIL resistance overcoming activity. Using several active compounds thus isolated, we investigated their effects on the expression of various proteins and mRNA involved in cancer progression, the influence of inducing apoptosis or cell viability. We have also elucidated the target molecules with respect to the remarkable active compound, fuligocandin B, which has TRAIL-overcoming activity obtained from a myxomycete species.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (40 results)

All 2017 2016 2015 2014 Other

All Int'l Joint Research (4 results) Journal Article (15 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 15 results,  Acknowledgement Compliant: 14 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 4 results,  Invited: 12 results) Book (4 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] クルナ大学/ダッカ大学(バングラデシュ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] コンケン大学(タイ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] クルナ大学/ダッカ大学(バングラデシュ)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] コンケン大学(タイ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Boesenberols, pimarane diterpenes with TRAIL resistance-overcoming activity from Boesenbergia pandurata2016

    • Author(s)
      Karmakar, U. K.; Ishikawa, N.; Arai, M. A.; Ahmed, F.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 8 Pages: 2075-2082

    • DOI

      10.1021/acs.jnatprod.6b00424

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Cerasoidine, a bis-aporphine alkaloid isolated from Polyalthia cerasoides during screening for Wnt signal inhibitors2016

    • Author(s)
      Shono, T.; Ishikawa, N.; Toume, K.; Arai, M. A.; Masu, H.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
    • Journal Title

      J. Nat. Prod.

      Volume: 79 Issue: 8 Pages: 2083-2088

    • DOI

      10.1021/acs.jnatprod.6b00409

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Synthesis of rocaglamide derivatives and evaluation of their Wnt signal inhibitory activities2016

    • Author(s)
      Arai, M. A.*; Kofuji, Y.; Tanaka, Y.; Yanase, N.; Yamaku, K.; Fuentes, R. G.; Karmakar, U. K.; Ishibashi, M.*
    • Journal Title

      Org. Biomol. Chem.

      Volume: 14 Issue: 11 Pages: 3061-3068

    • DOI

      10.1039/c5ob02537k

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Hes1 dimer inhibitor isolated by target protein oriented natural products isolation (TPO-NAPI) of differentiation activators of neural stem cells2016

    • Author(s)
      Arai, M. A.*; Ishikawa, N.; Tanaka, M.; Uemura, K.; Sugimitsu, N.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.*
    • Journal Title

      Chem. Sci.

      Volume: 7 Issue: 2 Pages: 1514-1520

    • DOI

      10.1039/c5sc03540f

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Valosin-containing Protein is a Target of 5'-l Fuligocandin B and Enhances TRAIL Resistance in Cancer Cells2016

    • Author(s)
      Arai, M. A.*; Taguchi, S.; Komatsuzaki, K.; Uchiyama, K.; Masuda, A.; Sampei, M.; Satoh, M.; Kado, S.; Ishibashi, M.*
    • Journal Title

      ChemistryOPEN

      Volume: 5 Issue: 6 Pages: 574-579

    • DOI

      10.1002/open.201600081

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells2015

    • Author(s)
      Fuentes, R. G.; Toume, K.; Arai, M. A.; Sadhu, S. K.; Ahmed, F.; Ishibashi, M.
    • Journal Title

      J. Nat. Prod.

      Volume: 11 Issue: 4 Pages: 864-872

    • DOI

      10.1021/np500933v

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 9-Hydorxycanthin-6-one, a β-carboline alkaloid from Eurycoma longifolia, is the first Wnt signal inhibitor through activation of GSK3β without depending on CK1α2015

    • Author(s)
      Ohishi, K.; Toume, K.; Arai, M. A.; Koyano, T.; Kowithayakorn, T.; Mizoguchi, T.; Itoh, M.; Ishibashi, M.
    • Journal Title

      J. Nat. Prod.

      Volume: 11 Issue: 5 Pages: 1139-1146

    • DOI

      10.1021/acs.jnatprod.5b00153

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sesquiterpenes with TRAIL-resistance overcoming activity from Xanthium strumarium2015

    • Author(s)
      Utpal K. Karmakar
    • Journal Title

      Bioorganic and Medicinal Chemistry

      Volume: 23 Issue: 15 Pages: 4746-4754

    • DOI

      10.1016/j.bmc.2015.05.044

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel cytotoxic isobenzofuran derivatives from Streptomyces sp. IFM 114902015

    • Author(s)
      Yixizhuoma; Tsukahara, K.; Toume, K.; Ishikawa, N.; Abdelfattah, M. S.; Ishibashi, M.
    • Journal Title

      Tetrahedron Lett.

      Volume: 56 Issue: 46 Pages: 6345-6347

    • DOI

      10.1016/j.tetlet.2015.09.116

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Boehmenan, a lignan, isolated from Hibiscus ficulneus showed Wnt signal inhibitory activity2015

    • Author(s)
      Takumi Shono
    • Journal Title

      Bioorganic and Medicinal Chemistry Letters

      Volume: 25 Issue: 14 Pages: 2735-2738

    • DOI

      10.1016/j.bmcl.2015.05.037

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prenylated flavonoids and resveratrol derivatives isolated from Artocarpus communis with the ability to overcome TRAIL resistance2015

    • Author(s)
      Kazufumi Toume
    • Journal Title

      Journal of Natural Products

      Volume: 78 Issue: 1 Pages: 103-110

    • DOI

      10.1021/np500734t

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Calotropin: a cardenolide from Calotropis gigantea that inhibits Wnt signaling by increasing casein kinase 1α in colon cancer cells2014

    • Author(s)
      Hyun Young Park
    • Journal Title

      ChemBioChem

      Volume: 15 Issue: 6 Pages: 872-878

    • DOI

      10.1002/cbic.201300786

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Ricinine: a pyridone alkaloid from Ricinus communis that activates the Wnt signaling pathway through casein kinase 1α2014

    • Author(s)
      Kensuke Ohishi
    • Journal Title

      Bioorganic Medicinal Chemistry

      Volume: 22 Issue: 17 Pages: 4597-4601

    • DOI

      10.1016/j.bmc.2014.07.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] がん関連シグナル経路を標的とした植物由来天然物の探索2014

    • Author(s)
      石橋正己
    • Journal Title

      化学と生物

      Volume: 52 Pages: 541-548

    • NAID

      130005090127

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ウィントシグナル調節を目指した生物活性天然物の探索2014

    • Author(s)
      當銘一文
    • Journal Title

      化学と生物

      Volume: 52 Pages: 731-741

    • NAID

      130005105744

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Search for bioactive constituents having effects on disease and development Pathways2017

    • Author(s)
      石橋正己
    • Organizer
      The 2nd international conference on herbal and traditional medicine (HTM2017)
    • Place of Presentation
      Bangkok (Thailand)
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 疾患シグナルに作用する天然物スクリーニング研究から2016

    • Author(s)
      石橋正己
    • Organizer
      理研シンポジウム-第17回分析・解析技術と化学の最先端
    • Place of Presentation
      理研(埼玉県和光市)
    • Year and Date
      2016-12-16
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 疾患シグナルに作用する天然物スクリーニング研究2016

    • Author(s)
      石橋正己
    • Organizer
      リグラリア研究会
    • Place of Presentation
      立教大学(東京都豊島区)
    • Year and Date
      2016-10-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Screening studies for natural products on disease and development pathways2016

    • Author(s)
      石橋正己
    • Organizer
      International Symposium on Natural Products for the Future 2016 (ISNPF2016)
    • Place of Presentation
      徳島文理大学(徳島県徳島市)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 変形菌成分フリゴキャンジンBの標的解析2016

    • Author(s)
      石橋正己
    • Organizer
      新学術領域研究「天然物ケミカルバイオロジー」研究成果報告シンポジウム
    • Place of Presentation
      慶応義塾大学(神奈川県横浜市)
    • Year and Date
      2016-07-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Natural products-based screening study on disease and development pathways2015

    • Author(s)
      Masami Ishibashi
    • Organizer
      Pacifichem 2015
    • Place of Presentation
      ハワイ
    • Year and Date
      2015-12-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] シグナル伝達調節作用をもつテルぺノイド成分の探索2015

    • Author(s)
      石橋正己
    • Organizer
      第59回香料・テルペンおよび精油化学に関する討論会
    • Place of Presentation
      近畿大学
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Bioactive natural products with TRAIL-resistance overcoming activity from medicinal plants of Bangladesh2015

    • Author(s)
      Firoj Ahmed
    • Organizer
      Inaugural Symposium of the Phytochemical Society of Asia 2015
    • Place of Presentation
      徳島文理大学
    • Year and Date
      2015-08-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経幹細胞分化活性化を目指した天然基盤分子の探索2015

    • Author(s)
      荒井緑
    • Organizer
      新学術領域研究「天然物ケミカルバイオロジー~分子標的と活性制御~」地区ミニシンポジウム・仙台
    • Place of Presentation
      仙台
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ウィントシグナル阻害作用をもつ天然物のスクリーニング2015

    • Author(s)
      石橋正己
    • Organizer
      天然有機化合物の生合成研究―新潟ミニシンポジウム―
    • Place of Presentation
      新潟大学駅南キャンパスときめいと
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Natural products screening studies targeting Wnt, Hedgehog, and TRAIL signaling pathways2014

    • Author(s)
      Masami Ishibashi
    • Organizer
      The 14th International Symposium on Traditional Medicine in Toyama 2014
    • Place of Presentation
      富山
    • Year and Date
      2014-10-28
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Natural products screening studies on Wnt and Hedgehog signaling pathways2014

    • Author(s)
      Masami Ishibashi
    • Organizer
      The 28th International Symposium on the Chemistry of Natural Products and the 8th International Conference on Biodiversity
    • Place of Presentation
      上海,中国
    • Year and Date
      2014-10-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Calotropis giantea およびXylocarpus granatum からのウィントシグナル阻害成分の探索2014

    • Author(s)
      當銘一文
    • Organizer
      第56回天然有機化合物討論会
    • Place of Presentation
      高知
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] Artocarpus communis由来のTRAIL耐性克服作用をもつプレニルフラボン成分2014

    • Author(s)
      石橋正己
    • Organizer
      第58回香料・テルペンおよび精油化学に関する討論会
    • Place of Presentation
      和歌山
    • Year and Date
      2014-09-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] バングラデシュ天然薬物資源調査2014

    • Author(s)
      石橋正己
    • Organizer
      第4回天然物パワーシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-07-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] パートナー天然物化学,改訂第3版(海老塚豊,森田博史,阿部郁朗編)2016

    • Author(s)
      石橋正己
    • Total Pages
      299
    • Publisher
      南江堂
    • Related Report
      2016 Annual Research Report
  • [Book] ウォーレン 有機化学 上 第2版(野依良治ら編)2015

    • Author(s)
      石橋正己
    • Total Pages
      728
    • Publisher
      東京化学同人
    • Related Report
      2015 Annual Research Report
  • [Book] 大学院講義有機化学Ⅱ(第2版) (野依良治ら編)2015

    • Author(s)
      石橋正己
    • Total Pages
      476
    • Publisher
      東京化学同人
    • Related Report
      2015 Annual Research Report
  • [Book] ウォーレン有機化学第2版(上)2015

    • Author(s)
      石橋正己
    • Total Pages
      682
    • Publisher
      東京化学同人
    • Related Report
      2014 Annual Research Report
  • [Remarks] 千葉大学大学院薬学研究院活性構造化学研究室

    • URL

      http://www.p.chiba-u.jp/lab/kassei/index.html

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report 2014 Annual Research Report
  • [Patent(Industrial Property Rights)] ナブセシンA、ナブセシンB、及びその製造方法2016

    • Inventor(s)
      石橋正己・原昇子・原康雅・石川直樹・酒井香奈江・五ノ井透
    • Industrial Property Rights Holder
      千葉大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-120162
    • Filing Date
      2016-06-16
    • Related Report
      2016 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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