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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23501324
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cancer epidemiology and prevention
• Research Institution: Health 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
• 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

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.

Research Products

• [Journal Article] Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in Apc ^<Min/+> mice (2014)
  • Author(s): Shimizu S, Fujii G, Takahashi M, Nakanishi R, Komiya M, Shimura M, Noma N, Onuma W, Terasaki M, Yano T, Mutoh M
  • Journal Title: J Clin Biochem Nutr Volume: 54 Pages: 95-101
  • DOI: 10.3164/jcbn.13-91
  • Peer Reviewed
• [Journal Article] The error-prone DNA polymerase ι provides quantitative resistance to lung tumorigenesis and mutagenesis in mice (2013)
  • Author(s): Iguchi M, Osanai M, Hayashi Y, Koentgen F, Lee GH
  • Journal Title: Oncogene advance online publication
  • DOI: 10.1038/onc.2013.331
  • Peer Reviewed
• [Journal Article] Chemical-induced Carcinogenesis (2013)
  • Author(s): Tanaka T, Shimizu M, Kochi T, Moriwaki H
  • Journal Title: J Exp Clin Med Volume: 5 Pages: 203-209
  • DOI: 10.1016/j.jecm.2013.10.009
  • Peer Reviewed
• [Journal Article] Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats (2013)
  • Author(s): Kochi T, Shimizu M, Ohno T, Baba A, Sumi T, Kubota M, Shirakami Y, Tsurumi H, Tanaka T, Moriwaki H
  • Journal Title: Int J Mol Sci Volume: 14 Pages: 14700-14711
  • DOI: 10.3390/ijms140714700
  • 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, Tanaka T
  • Journal Title: Carcinogenesis Volume: 34 Pages: 361-369
  • DOI: 10.1093/carcin/bgs348
  • Peer Reviewed
• [Journal Article] Combined antiproliferative effect of dietary PPARγ suppressing lipids fucoxanthinol and 1α,25-dihydroxyvitamin D_3 in human colon cancer cells (2012)
  • 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
  • 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
  • DOI: 10.2174/1389450111208041689
  • 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 2012 Volume: Article ID 658786 Pages: 16
  • DOI: 10.1155/2012/658786
  • 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
  • Year and Date: 20140328-30
• [Presentation] Functional roles of Wnt/β-catenin pathway regulating growth and maintenance of colonospheres (2014)
  • 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
  • Year and Date: 20140210-11
• [Presentation] Functional roles of CD44 and EpCAM in the development of colorectal cancer stem cells (2013)
  • Author(s): Terasaki M, Masuda S
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] 4'-Geranyloxyferulic acid-LNAME suppresses inflammation-associated colorectal carcinogenesis in mice (2013)
  • 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
  • Year and Date: 20131003-05
• [Presentation] Deoxycholic acid, secondary bile acid promotes AOM-induced colorectal carcinogenesis in distal colon of mice but not proximal colon (2013)
  • 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
  • Year and Date: 20131003-05
• [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
  • Year and Date: 20130606-08
• [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
  • Year and Date: 20130518-19
• [Presentation] Combined antiproliferative effect in dietary PPARγ regulating lipids against human colorectal cancer cells (2011)
  • 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
  • Year and Date: 20111114-17
• [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
  • Year and Date: 20110913-14
• [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
  • Year and Date: 20110831-0903
• [Remarks] 研究室のホームページ
  • URL: http://www3.hoku-iryo-u.ac.jp/courses/1/010/index.html