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2004 Fiscal Year Final Research Report Summary

Basic research for ‘gene-regulating chemoprevention' by using food factors

Research Project

Project/Area Number 14370126
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SAKAI Toshiyuki  Kyoto Prefectural University of Medicine, Department of Molecular-Targeting Cancer Prevention, Professor, 医学研究科, 教授 (20186993)

Co-Investigator(Kenkyū-buntansha) SOWA Yoshihiro  Kyoto Prefectural University of Medicine, Department of Molecular-Targeting cancer Prevention, Lecturer, 医学研究科, 講師 (70315935)
MATSUZAKI Youichirou  Kyoto Prefectural University of Medicine, Department of Molecular-Targeting Cancer Prevention, Assistant Professor, 医学研究科, 助手 (70282522)
YOSHIDA Tatsushi  Kyoto Prefectural University of Medicine, Department of Molecular-Targeting Cancer Prevention, Assistant Professor, 医学研究科, 助手 (80315936)
KAMIYAMA Jun  Meiji University of Oriental Medicine, Department of Surgery, Lecturer, 鍼灸学部, 講師 (20257538)
Project Period (FY) 2002 – 2004
Keywordsbutyrate / p18 / p19 / DR5 / TRAIL / I3C / TPA / p15
Research Abstract

Butyrate, a short chain fatty acid, represents one class of histone deacetylase(HDAC) inhibitors, and is an important molecule for preventing colorectal cancer. It is one of the most abundant short chain fatty acids found in the large intestine and is generated by bacterial fermentation of dietary fibers. We discovered that the HDAC inhibitors butyrate and trichostatin A(TSA) inhibit cellular proliferation and induce the expressions of p18^<INK4C> and p19^<INK4d> genes in p16^<INK4a>-deleted human T cell leukemia cell line Jurkat. Furthermore, we demonstrated that the HDAC inhibitors up-regulate the expression of death receptor 5(DR5), a receptor for tumor necrosis factor-related apoptosis-inducing ligand(TRAIL). HDAC inhibitors strongly sensitized exogenous soluble recombinant human TRAIL-induced apoptosis.
Indole-3-carbinol (I3C) is a naturally occurring compound found in vegetables such as broccoli and cauliflower, and has been shown to arrest human tumor cells in the G1 phase of the … More cell cycle. However, the molecular mechanism responsible for this effect has not been sufficiently elucidated. We found that I3C activates the cyclin-dependent kinase(CDK) inhibitor p15^<INK4b> gene through its promoter, accompanied by cell growth inhibition in HaCaT cells. Treatment with I3C almost did not affect the expressions of the other CDK inhibitors such as p19^<INK4d>, p21^<WAF1> and p27^<Kip1>. These results suggest that p15^<INK4b> is an important molecular target of I3C among CDK inhibitors.
p18^<INK4c> is a haploinsufficient tumor suppressor. We showed that 12-O-tetradecanoylphorbol-13-acetate(TPA), a tumor promoter, suppresses the expression of p18^<INK4c> through its promoter, accompanied by the induction of cell growth. Reduction of p18^<INK4c> using small interfering RNA also enhanced cell growth, implicating p18^<INK4c> as a critical target of TPA. Protein kinase C inhibitor and curcumin, an anti-tumor promoting agent, abrogated the effect of TPA on p18^<INK4c>. However, dominant negative c-Jun (TAM-67) did not inhibit it. These results suggest the possibility that a mouse two-stage carcinogenesis model using TPA might partially represent human carcinogenesis pathway related to RB. Less

  • Research Products

    (34 results)

All 2005 2004 2003 2002

All Journal Article (34 results)

  • [Journal Article] Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.2005

    • Author(s)
      Takagaki, N. et al.
    • Journal Title

      International Journal of Oncology 25

      Pages: 185-189

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway.2005

    • Author(s)
      Takagaki, N., Sowa, Y., Oki, T., Nakanishi, R., Yogosawa, S., Sakai, T.
    • Journal Title

      International Journal of Oncology 26

      Pages: 185-189

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genistein induces gadd45 gene and G2/M cell cycle arrest in the DU145 human prostate cancer cell line.2004

    • Author(s)
      Oki, T.et al.
    • Journal Title

      FEBS Letters 577

      Pages: 55-59

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Indole-3-carbinol (I3C) activates the cyclin-dependent kinase inhibitor p15^<INK4b> gene.2004

    • Author(s)
      Matsuzaki, Y. et al.
    • Journal Title

      FEBS Letters 576

      Pages: 137-140

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Trichostatin A activates p18^<INK4c> gene : Differential activation and cooperation with p19^<INK4d> gene.2004

    • Author(s)
      Yokota, T. et al.
    • Journal Title

      FEBS Letters 574

      Pages: 171-175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells.2004

    • Author(s)
      Nakata, S. et al.
    • Journal Title

      Oncogene 23

      Pages: 6261-6271

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of protein kinase C promotes human cancer cell growth through downregulation of p18^<INK4c>.2004

    • Author(s)
      Matsuzaki, Y. et al.
    • Journal Title

      Oncogene 23

      Pages: 5409-5414

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Histone deacetylase inhibitors activate INK4d gene through Sp1 site in its promoter.2004

    • Author(s)
      Yokota, T. et al.
    • Journal Title

      Oncogene 23

      Pages: 5340-5349

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Activation of protein kinase C promotes human cancer cell growth through downregulation of p18^<INK4c>.2004

    • Author(s)
      Matsuzaki, Y., Takaoka, Y., Hitomi, T., Nishino, H., Sakai, T.
    • Journal Title

      Oncogene 23

      Pages: 5409-5414

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Histone deacetylase inhibitors activate p19^<INK4d> gene through Sp1 site in its promoter.2004

    • Author(s)
      Yokota, T., Matsuzaki, Y., Miyazawa, K., Zindy, F., Roussel, M., Sakai, T.
    • Journal Title

      Oncogene 23

      Pages: 5340-5349

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Histone deacetylase inhibitors upregulate death receptor 5/TRAIL-R2 and sensitize apoptosis induced by TRAIL/APO2-L in human malignant tumor cells.2004

    • Author(s)
      Nakata, S., Yoshida, T., Horinaka, M., Shiraishi, T., Wakada, M., Sakai, T.
    • Journal Title

      Oncogene 23

      Pages: 6261-6271

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Trichostatin A activates p18^<INK4c> gene : Differential activation and cooperation with p19^<INK4d> gene.2004

    • Author(s)
      Yokota, T., Matsuzaki, Y., Sakai, T.
    • Journal Title

      FEBS Letters 574

      Pages: 171-175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Indole-3-carbinol(I3C) activates the cyclin-dependent kinase inhibitor p15^<INK4b> gene.2004

    • Author(s)
      Matsuzaki, Y., Koyama, M., Hitomi, T., Kawanaka, M., Sakai, T.
    • Journal Title

      FEBS Letters 576

      Pages: 137-140

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genistein induces gadd45 gene and G2/M cell cycle arrest in the DU145 human prostate cancer cell line.2004

    • Author(s)
      Oki, T., Sowa, Y., Hirose, T., Takagaki, N., Horinaka, M., Nakanishi, R., Yasuda, C., Yoshida, T., Kanazawa, M., Satomi, Y., Nishino, H., Miki, T., Sakai, T.
    • Journal Title

      FEBS Letters 577

      Pages: 55-59

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] p15^<INK4b> in HDAC inhibitor-induced growth arrest.2003

    • Author(s)
      Hitomi, T. et al.
    • Journal Title

      FEBS Letters 554

      Pages: 347-350

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 15-deoxy-Δ^<12,14>-prostaglandin J_2 induces apoptosis through activation of the CHOP gene in HeLa cells.2003

    • Author(s)
      Saito, S. et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 311

      Pages: 17-23

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] DNA damage induces transcriptional activation of p73 by removing C-EBPα repression on E2F1.2003

    • Author(s)
      Marabese, M. et al.
    • Journal Title

      Nucleic Acids Research 31

      Pages: 6624-6632

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] p53-independent induction of Gadd45 by histone deacetylase inhibitor : co-ordinate regulation by transcription factors Oct-1 and NF-Y.2003

    • Author(s)
      Hirose, T. et al.
    • Journal Title

      Oncogene 22

      Pages: 7762-7773

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regulation of the growth arrest and DNA damage-inducible gene 45 (GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells.2003

    • Author(s)
      Bruemmer, D. et al.
    • Journal Title

      Circulation Research 93

      Pages: 38-47

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isoliquiritigenin inhibits the growth of prostate cancer.2003

    • Author(s)
      Kanazawa, M. et al.
    • Journal Title

      European Urology 43

      Pages: 580-586

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Isoliquiritigenin inhibits the growth of prostate cancer.2003

    • Author(s)
      Kanazawa, M., Satomi, Y., Mizutani, Y., Ukimura, O., Kawauchi, A., Sakai, T., Baba, M., Okuyama, T., Nishino, H., Miki, T.
    • Journal Title

      European Urology 43

      Pages: 580-586

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regulation of the growth arrest and DNA damage-inducible gene 45(GADD45) by peroxisome proliferator-activated receptor gamma in vascular smooth muscle cells.2003

    • Author(s)
      Bruemmer, D., Yin, F., Liu, J., Berger, J.P., Sakai, T., Blaschke, F., Fleck, E., Van Herle, A.J., Forman, B.M., Law, R.E.
    • Journal Title

      Circulation Research 93

      Pages: 38-47

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] p53-independent induction of Gadd45 by histone deacetylase inhibitor : coordinate regulation by transcription factors Oct-1 and NF-Y.2003

    • Author(s)
      Hirose, T., Sowa, Y., Takahashi, S., Saito, S., Yasuda, C., Shindo, N., Furuichi, K., Sakai, T.
    • Journal Title

      Oncogene 22

      Pages: 7762-7773

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] DNA damage induces transcriptional activation of p73 by removing C-EBPα repression on E2F1.2003

    • Author(s)
      Marabese, M., Vikhankaya, F., Rainelli, C., Sakai, T., Broggini, M.
    • Journal Title

      Nucleic Acids Research 31

      Pages: 6624-6632

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 15-deoxy-Δ^<12,14>-prostaglandin J_2 induces apoptosis through activation of the CHOP gene in HeLa cells.2003

    • Author(s)
      Saito, S., Takahashi, S., Takagaki, N., Hirose, T., Sakai, T.
    • Journal Title

      Biochemical and Biophysical Research Communications 311

      Pages: 17-23

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] p15^<INK4b> in HDAC inhibitor-induced growth arrest.2003

    • Author(s)
      Hitomi, T., Matsuzaki, Y., Yokota, T., Takaoka, Y., Sakai, T.
    • Journal Title

      FEBS Letters 554

      Pages: 347-350

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] E7 proteins from oncogenic human papillomavirus types transactivate p73 : role in cervical intraepithelial neoplasia.2002

    • Author(s)
      Brooks, L.A. et al.
    • Journal Title

      British Journal of Cancer 86

      Pages: 263-268

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular cloning and characterization of the human p19^<INK4d> gene promoter.2002

    • Author(s)
      Matsuzaki, Y. et al.
    • Journal Title

      FEBS Letters 517

      Pages: 272-276

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The characterization of the human Siah-1 promoter.2002

    • Author(s)
      Maeda, A. et al.
    • Journal Title

      FEBS Letters 512

      Pages: 223-226

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Quercetin enhances tumorigenicity induced by N-Ethyl-N'-Nitro-N-Nitrosoguanidine in the duodenum of mice.2002

    • Author(s)
      Matsukawa, Y. et al.
    • Journal Title

      Environmental Health and Preventive Medicine 6

      Pages: 235-239

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Quercetin enhances tumorigenicity induced by N-Ethyl-N'-Nitro-N-Nitrosoguanidine in the duodenum of mice.2002

    • Author(s)
      Matsukawa, Y., Nishino, H., Yoshida, M., Sugihara, H., Katsura, K., Takamatsu, T., Okuzumi, J., Matsumoto, K., Sato-Nishimori, F., Sakai, T.
    • Journal Title

      Environmental Health and Preventive Medicine 6

      Pages: 235-239

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The characterization of the human Siah-1 promoter.2002

    • Author(s)
      Maeda, A., Yoshida, T., Kusuzaki, K., Sakai, T.
    • Journal Title

      FEBS Letters 512

      Pages: 223-226

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Molecular cloning and characterization of the human p19^<INK4d> gene promoter.2002

    • Author(s)
      Matsuzaki, Y., Miyazawa, K., Yokota, T., Hitomi, T., Yamagishi, H., Sakai, T.
    • Journal Title

      FEBS Letters 517

      Pages: 272-276

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] E7 proteins from oncogenic human papillomavirus types transactivate p73 : role in cervical intraepithelial neoplasia.2002

    • Author(s)
      Brooks, L.A., Sullivan, A., O'Nions, J., Bell, A., Dunne, B., Tidy, J.A., Evans, D.J., Osin, P., Vousden, K.H., Gusterson, B., Farrell, P.J., Storey, A., Gasco, M., Sakai, T., Crook, T.
    • Journal Title

      British Journal of Cancer 86

      Pages: 263-268

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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