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2002 Fiscal Year Final Research Report Summary

Development of the new cancer preventing method with the ingredient of the food of Kyoto

Research Project

Project/Area Number 12794011
Research Category

Grant-in-Aid for University and Society Collaboration

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

Principal Investigator

SAKAI Toshiyuki  Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Professor, 医学部, 教授 (20186993)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Tatsushi  Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (80315936)
MATSUZAKI Youichirou  Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (70282522)
SOWA Yoshihiro  Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Lecturer, 医学部, 講師 (70315935)
NOMURA Hitoshi  Chugai Pharmaceutical Co.Ltd. Research Div., Senior Scientist, 創薬研究担当部長
KAMIYAMA Jun  Kyoto Prefectural University of Medicine, Department of Preventive Medicine, Assistant Professor, 医学部, 助手 (20257538)
Project Period (FY) 2000 – 2002
KeywordsVitamin D_3 / p27 / NF-Y / mac25 / gadd45 / Sodium Butyrate / flavonoids / quercetin
Research Abstract

We showed clearly that the vitamin D_3 which is considered to have a preventive effect on colon cancer and prostatic cancer, etc, contained in the mushroom used abundantly at the food of Kyoto, activates the p27 gene promoter through its Sp1 and CCAAT binding sites by the transcription factors Sp1 and NF-Y, and not through the vitamin D_3 receptor-binding site.
Vitamin D_3 also activates mac25, gene, which is known to compensate for the function of tumor-suppressor gene p53.
The dietary fiber, which is contained in the root crop used in the food of Kyoto, is metabolized to butyrate. We showed clearly that the butyrate activates the gadd45 gene promoter, in p53-independent manner, through its Oct-1 and CCAAT binding sites by the transcription factors Oct-1 and NF-Y.
We searched for another drugs which can activate gadd45 gene promoter from the ingredients of food, such as flavonoids contained in the Kyoto vegetable, green tea, etc., and found that quercetin which is a kind of flavonoid activates gadd45 gene in p53-independent manner. Although this activation was seen in the mRNA level, there was no change in promoter activity. It has suggested that the mechanism of activation of gadd45 gene is different between butyrate and quercetin.
Using about 16 gene promoters we have (eg. cell cycle-regulating genes, apoptosis related genes), the promoter-activating drug was searched and some interesting drugs were found out. These drugs are expected to become new cancer preventive drugs.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kanemitsu, N., Kato, M.V., Miki, T., Komatsu, S., Okazaki, Y., Hayashizaki, Y., Sakai, T.: "Characterization of the promoter of the murine mac25 gene"Biochemical Biophysical and Research Communications. 279. 251-257 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Huang, L., Sowa, Y., Sakai, T., Pardee, A.B.: "Activation of the p21/WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp sites"Oncogene. 19. 5712-5719 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 酒井敏行, 神山順, 曽和義広: "発癌感受性に対する食物成分による分子修飾"癌の臨床. 46. 1421-1424 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sowa, Y., Sakai, T.: "Butyrate as a model for "gene-regulating chemoprevention and chemotherapy""Biofactors. 12. 283-287 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, S., Saito, S., Ohtani, N., Sakai, T.: "Involvement of the Oct-1 regulatory element of the gadd45 promoter in the p53-independent response to ultraviolet irradiation"Cancer Research. 61. 1187-1195 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanemitsu, N., Kato, M.V., Bai, F., Miki, T., Inoue, T., Sakai, T.: "Correlation between induction of the mac25 gene and antiproliferative effects of 1α,25(OH)_2-D_3 on breast cancer and leukemic cells"International Journal of Molecular Medicine. 7. 515-520 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onishi, K., Kato, M.V., Bai, F., Sakai, T.: "SMRT as a T3SF-binding protein"Int. J. Oncol.. 18. 985-989 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida, T., Maeda, A., Tani, N., Sakai, T.: "Promoter structure and transcription initiation sites of the human Death Receptor 5/TRAIL-R2 gene"FEBS Letters. 507. 381-385 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matikainen T, Perez GI, Jurisicova A, Pru JK, Schlezinger JJ, Ryu HY, Lame J, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH, Tilly JL.: "Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals"Nature Genet.. 28. 355-360 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda, A., Yoshida, T., Kusuzaki, K., Sakai, T.: "The characterization of the human Siah-1 promoter"FEBS Letters. 512. 223-226 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsukawa, Y., Nishino, H., Yoshida, U., Sugihara, H., Katsura, K., Takamatsu, T., Okuzumi, J., Matsumoto, K., Sato-Nishimori, F., Sakai, T.: "Quercetin enhances tumorigenicity induced by N-Ethyl-N'-Nitro-N-Nitrosoguanidine in the duodenum of mice"Environmental Health and Preventive Medicine. 6. 235-239 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuzaki, Y., Miyazawa, K., Yokota, T., Hitomi, T., Yamagishi, H., Sakai, T.: "Molecular cloning and characterization of the human p19^<INK4d> gene promoter"FEBS Letters. 517. 272-276 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 神山順, 酒井敏行: "遺伝子調節化学予防-発癌の遺伝子異常に基づいた新しい予防法の開発-"医学のあゆみ. 204. 3-6 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanazawa, M., Satomi, V., Mizutani, Y., Ukimura, O., Kawauchi, A., Sakai, T., Baba, M., Okuyama, T., Nishino, H., Miki, T.: "Isoliquiritigenin inhibits the growth of prostate cancer"Eur. Urol.. (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsukawa, Y., Sato, F., Sakai, T.: "Effects of flavonoids on cell cycle and differentiation in cancer cells. Proceedings of International Conference on Food Factors-Chemistry and Cancer Prevention-(Osawa, T., editor)"Tokyo : Springer-Verlag (In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 酒井敏行: "がん化学予防の最前線.西野輔翼編"大阪:医療ジャーナル社. 106 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanemitsu,N., Kato,M.V., Miki,T., Komatsu,S., Okazaki,Y., Hayashizaki,Y., and Sakai,T.: "Characterization of the promoter of the murine mac25 gene"Biochemical Biophysical and Research Communications. 279. 251-257 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Huang,L., Sowa,Y., Sakai,T., and Pardee,A.B.: "Activation of the p21/WAF1/CIP1 promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites"Oncogene. 19. 5712-5719 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sowa,Y., Sakai,T.: "Butyrate as a model for "gene-regulating chemoprevention and chemotherapy""Biofactors. 12. 283-287 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi,S., Saito,S., Ohtani,N., and Sakai,T.: "Involvement of the Oct-1 regulatory element of the gadd45 promoter in the p53-independent response to ultraviolet irradiation"Cancer Research. 61. 1187-1195 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanemitsu,N., Kato,M.V., Bai,F, Miki,T., Inoue,T., and Sakai,T.: "Correlation between induction of the mac25 gene and antiproliferative effects of 1α25(OH)2-D_3 on breast cancer and leukemic cells"International Journal of Molecular Medicine. 7. 515-520 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onishi,K., Kato,M.V., Bai,F, Sakai,T.: "SMRT as a T3SF-binding protein"International Journal of Oncology. 18. 985-989 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida,T., Maeda,A., Tani,N., and Sakai,T.: "Promoter structure and transcription initiation sites of the human Death Receptor 5/TRAIL-R2 gene"FEBS Letters. 507. 381-385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matikainen,T., Perez,G.I., Jurisicova,A., Pru,J.K., Schlezinger,J.J., Ryu,H.Y., Laine,J., Sakai,T., Korsmeyer,S.J., Casper,R.F., Sherr,D.H., and Tilly,J.L.: "Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals"Nature Genetics. 28. 355-360 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsukawa,Y., Nishino,H., Yoshida,M., Sugihara,H., Katsura,K., Takamatsu,T., Okuzumi,J., Matsumoto,K., Sato-Nishimori,F., and Sakai,T.: "Quercetin enhances tumorigenicity induced by N-Ethyl-N'-Nitro-N-Nitrosoguanidine in the duodenum of mice"Environmental Health and Preventive Medicine. 6. 235-239 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda,A., Yoshida,T., Kusuzaki,K., and Sakai,T.: "The characterization of the human Siah-1 promoter"FEBS Letters. 512. 223-226 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuzaki,Y., Miyazawa,K., Yokota,T., Hitomi,T., Yamagishi,H., and Sakai,T.: "Molecular cloning and characterization of the human p19INK4d gene promoter"FEBS Letters. 517. 272-276 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanazawa,M., Satomi,Y., Mizutani,Y., Ukimura,O., Kawauchi,A., Sakai,T., Baba,M., Okuyama,T., Nishino,H., and Miki,T.: "Isoliquiritigenin inhibits the growth of prostate cancer"Eur. Urol.. In press. 2003

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

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Published: 2004-04-14  

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