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Nuclear receptors as molecular regulator and chemopreventive targets of colon cancer stem cells.

Research Project

Project/Area Number 23501324
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cancer epidemiology and prevention
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

MASUDA Sonoko  北海道医療大学, 薬学部, 教授 (90157206)

Co-Investigator(Kenkyū-buntansha) TANAKA Takuji  岐阜大学, 医学部, 非常勤講師 (40126743)
OSANAI Makoto  高知大学, 教育研究部・医療学系, 准教授 (60381266)
TERASAKI Masaru  北海道医療大学, 薬学部, 講師 (10391195)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords大腸がん幹細胞 / 核内受容体 / がん化学予防 / 分子標的治療 / ビタミンD / カロテノイド / 分子イメージング / がん遺伝子 / 薬物代謝酵素 / がん幹細胞標的分子 / ビタミンD / フコキサンチノール / VDR / PPARG / RAR
Research Abstract

Increasing evidence suggests that colon cancer stem cells (CCSC) have responsible for carcinogenesis, cancer development and recurrence. To establish signaling pathways in CCSC, which are implicated in the initiation and progression of colon cancer, we examined nuclear receptor signaling in colonospheres that are enriched in CCSC from established cell lines. We found that colonospheres formed by colon cancer cell lines are highly enriched in CCSC and that Wnt/b-catenin pathway plays a critical role in growth and maintenance of colonospheres. We also found that the combination of Fucoxanthinol and 1a,25-dihydroxyvitamin D3 acts on the CCSC cell growth through down-regulation of PPARg and NFkB p52, and as an intrinsic factor for the prevention of colon cancer. These findings establish a critical role for PPARg and vitamin D receptor (VDR) in growth regulation in colon cancer cells via functionally relevant cross-talk between these nuclear signaling pathways.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (39 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (28 results) Remarks (1 results)

  • [Journal Article] Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in <i>Apc</i><sup>Min/+</sup> mice2014

    • Author(s)
      Shimizu S, Fujii G, Takahashi M, Nakanaishi R, Komiya M, Shimura M, Noma N, Onuma W, Yano T, Mutoh M.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 54 Issue: 2 Pages: 95-101

    • DOI

      10.3164/jcbn.13-91

    • NAID

      130004879356

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The error-prone DNA polymerase ι provides quantitative resistance to lung tumorigenesis and mutagenesis in mice2013

    • Author(s)
      Iguchi M, Osanai M, Hayashi Y, Koentgen F, Lee GH
    • Journal Title

      Oncogene advance online publication

      Volume: 33 Issue: 27 Pages: 3612-3617

    • DOI

      10.1038/onc.2013.331

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemical-induced Carcinogenesis.2013

    • Author(s)
      Takuji Tanaka, Masahito Shimizu, Takahiro Kochi, and Hisataka Moriwaki
    • Journal Title

      J. Exp. Clin. Med.

      Volume: 5 Issue: 6 Pages: 203-209

    • DOI

      10.1016/j.jecm.2013.10.009

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats.2013

    • Author(s)
      Takahiro Kochi, Masahito Shimizu, Tomohiko Ohno, Atsushi Baba, Takafumi Sumi, Masaya Kubota, Yohei Shirakami, Hisashi Tsurumi, Takuji Tanaka, and Hisataka Moriwaki
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 14 Issue: 7 Pages: 14700-14711

    • DOI

      10.3390/ijms140714700

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice.2013

    • Author(s)
      Kuno, T., Hatano, Y., Tomita, H., Hara, A., Hirose, Y., Hirata, A., Mori, H., Terasaki, M, Masuda, S., and Tanaka, T.
    • Journal Title

      Carcinogenesis

      Volume: 34 Issue: 2 Pages: 361-369

    • DOI

      10.1093/carcin/bgs348

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined antiproliferative effect of dietary PPARγ suppressing lipids fucoxanthinol and 1α,25-dihydroxyvitamin D_3 in human colon cancer cells2012

    • Author(s)
      Terasaki M, Nagao A, Maeda H, Miyashita K, Masuda S
    • Journal Title

      Carotenoid Sci

      Volume: 17 Pages: 40-43

    • URL

      http://www.carotenoid.jp

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Animal models of carcinogenesis in inflamed colorectum : potential use in chemoprevention study2012

    • Author(s)
      Tanaka T
    • Journal Title

      Curr Drug Targets

      Volume: 13 Pages: 1689-1697

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of an inflammation-associated colorectal cancer model and its application for research on carcinogenesis and chemoprevention.2012

    • Author(s)
      Tanaka, T.
    • Journal Title

      Int. J. Inflam.

      Volume: 2012 Pages: 1-16

    • DOI

      10.1155/2012/658786

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined antiproliferative effect of dietary PPARγ suppressing lipids fucoxanthinol and 1α,25-dihydroxyvitamin D3 in human colon cancer cells.2012

    • Author(s)
      Terasaki, M., Nagao, A., Maeda, H., Miyashita, K., and Masuda, S.
    • Journal Title

      Carotenoid Sci.

      Volume: 17 Pages: 40-43

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Animal models of carcinogenesis in inflamed colorectum: potential use in chemoprevention study.2012

    • Author(s)
      Tanaka, T.
    • Journal Title

      Curr. Drug Targets

      Volume: 13 Pages: 1689-1697

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] CD44発現と大腸がん幹細胞形質の相関性2014

    • Author(s)
      寺崎将、増田園子
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] Functional roles of Wnt/β-catenin pathway regulating growth and maintenance of colonospheres2014

    • Author(s)
      Masuda S, Inoue S, Ohmura Y, Ono M, Takagi K, Nakagawa M, Nakamura K, Mikami Y, Yamamoto S, Sawada K, Hamazaki Y, Maeda S, Terasaki M
    • Organizer
      4^<th> International Symposium on Carcinogenic Spiral
    • Place of Presentation
      Sapporo
    • Related Report
      2013 Final Research Report
  • [Presentation] CD44 発現と大腸がん幹細胞形質の相関性2014

    • Author(s)
      寺崎 将、増田園子
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] : Functional roles of Wnt/β-catenin pathway regulating growth and maintenance of colonospheres.2014

    • Author(s)
      S. Masuda, S. Inoue, Y. Ohmura, M. Ono, K. Takagi, M. Nakagawa, K. Nakamura, Y. Mikami, S. Yamamoto, K. Sawada, Y. Hamazaki, S. Maeda, and M. Terasaki
    • Organizer
      4th International Symposium on Carcinogenic Spiral
    • Place of Presentation
      Sapporo
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス大腸発癌に及ぼすデオキシコール酸の影響2014

    • Author(s)
      久野壽也、田中卓二、内木 綾、佐藤慎哉、鈴木周五、高橋 智
    • Organizer
      第30回日本毒性病理学会総会及び学術集会
    • Place of Presentation
      徳島
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional roles of CD44 and EpCAM in the development of colorectal cancer stem cells2013

    • Author(s)
      Terasaki M, Masuda S
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 4'-Geranyloxyferulic acid-LNAME suppresses inflammation-associated colorectal carcinogenesis in mice2013

    • Author(s)
      Tanaka T, Kochi T, Shimizu M, Sugie S, Moriwaki H
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] Deoxycholic acid, secondary bile acid promotes AOM-induced colorectal carcinogenesis in distal colon of mice but not proximal colon2013

    • Author(s)
      Kuno T, Tanaka T, Takamatsu M, Hatano Y, Tomita H, Hirose Y, Hirata A, Hara A
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] ニコチンはレチノイン酸代謝酵素CYP26A1の発現を低下させ乳癌の進行を抑制する2013

    • Author(s)
      小山内誠、李康弘
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] 分子イメージングによるがん幹細胞の特性解析2013

    • Author(s)
      加藤雄也、工藤成美、佐藤永楽、佐藤隆太郎、舘岡さおり、近野優、西川亮太、田中耕太、寺崎将、増田園子
    • Organizer
      日本薬学会北海道支部第140回例会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Functional roles of CD44 and EpCAM in the development of colorectal cancer stem cells.2013

    • Author(s)
      Masaru Terasaki and Sonoko Masuda
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report
  • [Presentation] : C57BL/KsJ-db/db-ApcMin/+ mice are useful model animals for investigating colorectal carcinogenesis associated with obesity and diabetes.2013

    • Author(s)
      Masaya Kubota, Hata Kazuya, Masahito Shimizu, Atsushi Baba, Tomohiko Ohno, Takahiro Kochi, Yohei Shirakami, Takuji Tanaka, Hisataka Moriwaki
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report
  • [Presentation] 4’-Geranyloxyferulic acid-L-NAME suppresses inflammation-associated colorectal carcinogenesis in mice.2013

    • Author(s)
      Takuji Tanaka, Takahiro Kochi, Masahito Shimizu, Shigeyuki Sugie, and Hisataka Moriwaki
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report
  • [Presentation] Deoxycholic acid, secondary bile acid promotes AOM-induced colorectal carcinogenesis in distal colon of mice but not proximal colon.2013

    • Author(s)
      Toshiya Kuno, Takuji Tanaka, Manabu Takamatsu, Yuichiro Hatano, Hiroyuki Tomita, Yoshinobu Hirose, Akihiro Hirata, and Akira Hara
    • Organizer
      72nd Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Yokohama
    • Related Report
      2013 Annual Research Report
  • [Presentation] 4’-Geranyloxyferulic acid-L-NAME suppresses inflammation-associated colorectal carcinogenesis in mice.2013

    • Author(s)
      Takuji Tanaka, Takahiro Kochi, Takayuki Mori, Masahito Shimizu, and Hisataka Moriwaki
    • Organizer
      第20回日本がん予防学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト大腸がん幹細胞の単離と特性解析2013

    • Author(s)
      西川亮太、近野 優、舘岡さおり、佐藤隆太郎、佐藤永楽、工藤成美、加藤雄也、田中耕太、寺崎 将、増田園子
    • Organizer
      日本薬学会北海道支部第140回例会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Cancer stem cell標的薬の迅速評価法の開発2013

    • Author(s)
      田中耕太、加藤雄也、工藤成美、佐藤永楽、佐藤隆太郎、舘岡さおり、近野 優、西川亮太、寺崎 将、増田園子
    • Organizer
      日本薬学会北海道支部第140回例会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Fucoxanthinolによる大腸がん幹細胞アポトーシス誘導作用とそのメカニズム2013

    • Author(s)
      寺崎 将、前多隼人、増田園子
    • Organizer
      日本ビタミン学会第65回大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] Combined antiproliferative effect in dietary PPARγ regulating lipids against human colorectal cancer cells2011

    • Author(s)
      Terasaki M, Maeda H, Hosokawa M, Miyashita K, Masuda S
    • Organizer
      International Society for Nutraceuticals and Functional Foods (ISNFF)
    • Place of Presentation
      Sapporo
    • Related Report
      2013 Final Research Report
  • [Presentation] フコキサンチンと活性型ビタミンD_3の複合効果による大腸がん化学予防法の開発2011

    • Author(s)
      寺崎将、長尾昭彦、前多隼人、宮下和夫、増田園子
    • Organizer
      第25回カロテノイド研究談話会
    • Place of Presentation
      筑波
    • Related Report
      2013 Final Research Report
  • [Presentation] 機能性脂質によるPPARγ発現抑制2011

    • Author(s)
      寺崎将、増田園子
    • Organizer
      平成23年度がん若手研究者ワークショップ
    • Place of Presentation
      蓼科
    • Related Report
      2013 Final Research Report
  • [Presentation] Combined antiproliferative effect in dietary PPARγ regulating lipids against human colorectal cancer cells.2011

    • Author(s)
      Masaru Terasaki, Hayato Maeda, Masahi Hosokawa, Kazuo Miyashita, Sonoko Masuda
    • Organizer
      International Society for Nutraceuticals and Functional Foods (ISNFF)
    • Place of Presentation
      Sapporo
    • Related Report
      2011 Research-status Report
  • [Presentation] Organomagnesium suppresses inflammation-associated colon carcinogenesis in male Crj: CD-1 mice.2011

    • Author(s)
      Kuno Toshiya, Hiroyuki, Tomita, Yuichiro Hatano, Akira Hara, Hideki Mori, Masaru Terasaki, Sonoko Masuda, Takuji Tanaka
    • Organizer
      70th Annual Meeting of the Japanese Cancer Association,
    • Place of Presentation
      Nagoya
    • Related Report
      2011 Research-status Report
  • [Presentation] フコキサンチンと活性型ビタミンD3による複合的大腸がん細胞増殖抑制の作用解析2011

    • Author(s)
      寺崎 将, 長尾昭彦, 田中卓二, 細川雅史, 宮下和夫, 増田園子
    • Organizer
      日本ビタミン学会第63回大会
    • Place of Presentation
      広島
    • Related Report
      2011 Research-status Report
  • [Presentation] ヒト大腸がん幹細胞様細胞の同定とその性質

    • Author(s)
      寺崎 将, 太田友子, 近藤雄介, 寺嶋 望, 中島聖太, 南 寿憲, 安田友香, 太田史子, 前多隼人, 増田園子
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] A highly polar xanthophyll of fucoxanthinol induces apoptosis in colonospher.

    • Author(s)
      Masaru Terasaki, and Sonoko Masuda
    • Organizer
      The 71th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      Sapporo
    • Related Report
      2012 Research-status Report
  • [Presentation] PPARγ抑制によるフコキサンチノールの大腸がん細胞増殖抑制効果

    • Author(s)
      寺崎 将, 前多隼人, 増田園子
    • Organizer
      日本ビタミン学会第64回大会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Research-status Report
  • [Presentation] ホウレン草由来 9’-cis-Neoxanthinによる大腸がん細胞増殖抑制作用機序

    • Author(s)
      寺崎 将, 太田友子, 太田史子, 近藤雄介, 寺嶋 望, 中島聖太, 南 寿憲, 安田友香, 増田園子
    • Organizer
      日本薬学会北海道支部第138回例会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Remarks] 研究室のホームページ

    • URL

      http://www3.hoku-iryo-u.ac.jp/courses/1/010/index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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