2004 Fiscal Year Final Research Report Summary
Basic research for ‘gene-regulating chemoprevention' by using food factors
| Project/Area Number |
14370126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SAKAI Toshiyuki Kyoto Prefectural University of Medicine, Department of Molecular-Targeting Cancer Prevention, Professor, 医学研究科, 教授 (20186993)
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| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | butyrate / p18 / p19 / DR5 / TRAIL / I3C / TPA / p15 |
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| 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
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Research Products
(34 results)
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[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.
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Journal Title
International Journal of Oncology 26
Pages: 185-189
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Oncogene 23
Pages: 5340-5349
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Oncogene 23
Pages: 6261-6271
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
FEBS Letters 577
Pages: 55-59
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
European Urology 43
Pages: 580-586
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Circulation Research 93
Pages: 38-47
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Oncogene 22
Pages: 7762-7773
Description
「研究成果報告書概要(欧文)」より
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[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.
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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
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[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.
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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
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[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.
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Journal Title
FEBS Letters 517
Pages: 272-276
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
British Journal of Cancer 86
Pages: 263-268
Description
「研究成果報告書概要(欧文)」より
