Examination of the effect of DIF, an inhibitor of G1 phase transition derived from Dictyostelium, as a new anti-cancer drug.

• Project/Area Number: 21590284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kyushu University
• Principal Investigator: TAKAHASHI Fumi 九州大学, 医学研究院, 講師 (50274436)
• Co-Investigator(Kenkyū-buntansha): WATANABE Yutaka 愛媛大学, 理工学研究科, 教授 (40114722)
• Co-Investigator(Renkei-kenkyūsha): MINAKO Hirahashi 九州大学, 大学病院, 医員 (90529877)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 抗腫瘍薬 / サイクリンD1 / G1期特異的 / Wntシグナル伝達経路 / モデル動物 / Wntシグナル伝達系

Research Abstract

Differentiation-inducing factor-1(DIF-1), a morphogen of Dictyostelium discoideum, shows anti-tumor effect in several human tumor cells in vitro. To evaluate whether DIF-1 is applicable for the treatment of tumor in vivo, the pharmacodynamics and the effect of DIF-1 in mice were analyzed.

Research Products

• [Journal Article] DIF-1 Inhibits the Wnt/β-catenin Signaling Pathway by Inhibiting TCF7L2 Expression in Colon Cancer Cell Lines (2012)
  • Author(s): Fan, X., TakahashiYanaga, F., Morimoto, S., Zhan, D.-Y., Igawa, K., Tomooka, K., & Sasaguri, T
  • Journal Title: Biochemical Pharmacology Volume: 83(1) Issue: 1 Pages: 47-56
  • DOI: 10.1016/j.bcp.2011.10.001
  • Peer Reviewed
• [Journal Article] Celecoxib and 2, 5-dimethyl-celecoxib prevent cardiac remodeling inhibitiAkt-mediated signal transduction in an inherited DCM mouse model (2011)
  • Author(s): Fan, X., Takahashi-Yanaga, F., Morimoto, S., Zhan, D.-Y., Igawa, K., Tomooka, K., & Sasaguri, T
  • Journal Title: Exp. Ther Volume: 338(1) Issue: 1 Pages: 2-11
  • DOI: 10.1124/jpet.111.179325
  • Peer Reviewed
• [Journal Article] Targeting Wnt Signaling : Can We Safely Eradicate Cancer Stem Cells? Crin (2010)
  • Author(s): Takahashi-Yanaga, F. & Kahn, M
  • Journal Title: Cancer Res Volume: 16(12) Pages: 3153-3162
  • Peer Reviewed
• [Journal Article] Anti-angiogenic effectdifferentiation-inducing factorinvolving VEGFR-2 expression inhibition independent of the Wnt/beta-catenin signaling pathway (2010)
  • Author(s): Yoshihara, T., Takahashi-Yanaga, F., Shiraishi, F., Morimoto, S., Watanabe, Y., Hirata, M., Hoka, S., & SasaguriT
  • Journal Title: Mol. Cancer Volume: 9(1) Pages: 245-245
  • Peer Reviewed
• [Journal Article] Dictyostelium differentiation-inducing factor-l binds to mitochondrial ma late dehydrogenase and inhibits its activity (2010)
  • Author(s): Matsuda, T., Takahashi-Yanaga, F., Yoshihara, T., Maenaka, K., Watanabe, Y., Miwa, Y., Morimoto, S., Kubohara, Y., Hirata, M., & Sasaguri, T
  • Journal Title: J. Pharmacol. Sci Volume: 112(3) Pages: 320-326
  • Peer Reviewed
• [Journal Article] Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2expression inhibition independent of the Wnt/ss-catenin signaling pathway. (2010)
  • Author(s): Yoshihara T, Takahashi-Yanaga F, Shiraishi F, Morimoto S, Watanabe Y, Hirata M, Hoka S, Sasaguri T.
  • Journal Title: Mol Cancer. Volume: 9 Pages: 245-245
  • Peer Reviewed
• [Journal Article] Targeting Wnt signaling : can we safely eradicate cancer stem cells? (2010)
  • Author(s): Takahashi-Yanaga F, Kahn M.
  • Journal Title: Clin Cancer Res. Volume: 16(12) Pages: 3153-62
  • Peer Reviewed
• [Journal Article] Dictyostelium differentiation-inducing factor-1 binds to mitochondrial malate dehydrogenase and inhibits its activity (2010)
  • Author(s): Matsuda, T., Takahashi-Yanaga, F., Yoshihara, T., Maenaka, K., Watanabe, Y., Miwa, Y., Morimoto, S., Kubohara, Y., Hirata, M., Sasaguri, T.
  • Journal Title: J Pharmacol Sci. 112 Pages: 320-326
  • NAID: 10027744481
  • Peer Reviewed
• [Journal Article] Celecoxib and 2,5-dimethyl-celecoxib prevent cardiac remodeling inhibiting Akt-mediated signal transduction in an inherited DCM mouse model
  • Author(s): Fan X, Takahashi-Yanaga F, Morimoto S, Zhan D.-Y, Igawa K, Tomooka K, Sasaguri T.
  • Journal Title: Journal of Pharmacology and Experimental Therapeutics Volume: 印刷中
  • Peer Reviewed
• [Presentation] The inhibition of DUSP-1 expressionenhancesanti-tumor effects of differentiation-inducing factor-1 inHeLa eel 1s<DUSP-1発現抑制にdifferentiation-inducingfactor-1抗腫瘍活性の増強効果〉 (2012)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第85回日本薬理学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-15
• [Presentation] DUSP-1の抑制によりdifferentiation-inducing factor-1の抗腫瘍効果は増強する (2012)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第85回日本薬理学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-15
• [Presentation] 細胞性粘菌由来分化誘導因子DIF-1ははト大腸癌由来HCT-116細胞においてc-Mycの発現を低下させる (2012)
  • Author(s): 神宮司健太郎、高橋富美、中村俊央、笹栗俊之
  • Organizer: 第85回日本薬理学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] 細胞性粘菌由来分化誘導因子DIF-1はヒト大腸癌由来HCT-116細胞においてc-Mycの発現を低下させる (2012)
  • Author(s): 神宮司健太郎、高橋富美、中村俊央、笹栗俊之
  • Organizer: 第85回日本薬理学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] DUSP-1の抑制によりdifferentiation-inducingfactor-1の抗腫瘍効果は増強する (2011)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第32回日本臨床薬理学会年会
  • Place of Presentation: 浜松
  • Year and Date: 2011-12-02
• [Presentation] DUSP-1の抑制によりdifferentiation-inducing factor-1の抗腫瘍効果は増強する (2011)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第32回日本臨床薬理学会年会(12/1-3:浜松)
  • Place of Presentation: 浜松
  • Year and Date: 2011-12-02
• [Presentation] Differentiation-inducingfactor-1inhibitstheWntsignalingpathwaybyreducingTCF7L2expressionincoloncancercells (2011)
  • Author(s): Jingushi, K., Takahashi, F., SasaguriT
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Differentiation-inducing factor-1 inhibits the Wnt signaling pathway by reducing TCF7L2 expression in colon cancer cells (2011)
  • Author(s): Jingushi, K., Takahashi, F., Sasaguri, T.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] DUSP-1の抑制によりdifferentiation-inducingfactor-1の抗腫瘍効果は増強する (2011)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Wntシグナル阻害剤Differentiation-inducingfactor-1の抗腫瘍活性の検討 (2011)
  • Author(s): 高橋富美、吉原達也、笹栗俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] Wntシグナル阻害剤Differentiation-inducing factor-1の抗腫瘍活性の検討 (2011)
  • Author(s): 高橋富美、吉原達也、笹栗俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] DUSP-1の抑制によりdifferentiation-inducing factor-1の抗腫瘍効果は増強する (2011)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 酸化ストレス誘発小腸腫瘍に対するDifferentiation-inducingfactor-1の抗腫瘍効果 (2010)
  • Author(s): 高橋富美、吉原達也、中津可道、績輝久、中別府雄作、笹栗俊之
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 酸化ストレス誘発小腸腫瘍に対するDifferentiation-inducing factor-1の抗腫瘍効果 (2010)
  • Author(s): 高橋富美、吉原達也、中津可道、續輝久、中別府雄作、笹栗俊之
  • Organizer: 第69回 日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Differentiation-inducingfactor-1はVEGFR2の発現を低下させることによりin vitroおよびinvivoにおいて血管新生を阻害する (2009)
  • Author(s): 吉原達也、高橋富美、笹栗俊之
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Differentiation-inducing factor-1はVEGFR2の発現を低下させることにより in vitro および in vivo において血管新生を阻害する (2009)
  • Author(s): 吉原達也, 高橋寓美, 笹栗俊之
  • Organizer: 第68回日本癌学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01