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Radiosensitization by inhibition of cell survival signal

Research Project

Project/Area Number 18591388
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionIbaraki Prefectural University of Health Science

Principal Investigator

KUBOTA Nobuo  Ibaraki Prefectural University of Health Science, Department of Radiological Sciences, Professor (20046139)

Co-Investigator(Kenkyū-buntansha) SHIKANO Naoto  Ibaraki Prektural University of Health Sciences, Department of Radiological Sciences, Assistant Professor (80295435)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsRdiosensitization / Sulforaphane / pancreatic cell line / apoptosis / Apaf-1 / 生存シグナル / 放射線増感効果 / apigenin / Bcl-2 / Apaf-1
Research Abstract

Sulforaphane (SFN), an isothiocyanate present in broccoli, is one of the most promising chemopreventive agents. It inhibits cell proliferation and induces apoptosis in different tumor cell lines, suggesting that SFN might be useful as chemotherapeutic agent for cancer treatment. In this study, we investigated the radiosensitizing effect of SFN in two human pancreatic cancer cell lines, MIA PaCA-2 and PANC-1. Radiation survival curves obtained showed that SFN radiosensitized both cell lines, but potentiated X-ray sensitivity more in MIAPaCa-2 than PANC-1 cells. In addition, SFN radiosensitized MIA PaCA-2 cells to apoptosis, but not PANC-1. The results obtained indicates that SFN-mediated radiosensitization by inducing apoptosis in MIA PaCa-2 cells is not regulated by Bc1-2 and Bax. A combined treatment of SFN and X-rays resulted in a decrease in the level of XIAP in both cells. MIA PaCa-2 cells treated with SFN and X-rays exhibited a marked increase in protein level of Apaf-1, which is essential for activation of.caspase-9. These results indicate that Apaf-1 is an important role in SFN-induced radiosensization by inducing apoptosis. Thus, SFN appears to be a promising radiosensitizing agent for use against human carcinomas.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2008 2007 2006

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (3 results) Book (2 results)

  • [Journal Article] The chemopreventive flavonoid apigeninconfers radiosensitizing effectin human tumor cells grown as monolyer s and spheroids2007

    • Author(s)
      Norihiro Watanabe, Ryoichi Hirayama, Nobuo Kubota
    • Journal Title

      J Radiat Res 48

      Pages: 45-50

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The chemopreventive flavonoid apigeninconfers radiosensitizing effectin human tumor cells grown as monolyer s and spheroids2007

    • Author(s)
      Norihiro, Watanabe, Ryoichi, Hirayama, Nobuo, Kubota
    • Journal Title

      J Radiat Res 48

      Pages: 45-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The chemopreventive flavonoid apigeninconfers radiosensitizing effectin human tumor cells grown as monolyer s and spheroids.2007

    • Author(s)
      Norihiro Watanabe, Ryoichi Hirayama, Nobuo Kubota
    • Journal Title

      J Radiat Res 48

      Pages: 45-50

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids.2007

    • Author(s)
      Norihiro Watanabe, Ryoichi Hirayama, Nobuo Kubota
    • Journal Title

      J Radiat Res 48(1)

      Pages: 45-50

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Heat shock protein 90 inhibitor geldanamycin and 17AAG as anti-cancer therapeutic agents2006

    • Author(s)
      Nobuo Kubota, Yoshitaka Matsumoto, Hikaru Machida
    • Journal Title

      Jpn J Hyperthermic Oncol 22

      Pages: 201-210

    • NAID

      10019596792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of homologous recombination repair in irreadiated tumor cells pretreated with Hsp90 inhibiotr 17-allylamino-17-demethoxygeldanamycin.2006

    • Author(s)
      Noguchi M, Yu D, Hirayama R, Ninomiya Y, Sekine E, Kubota N, Ando K, Okayasu R
    • Journal Title

      Biochem Biophys Res Commun 351

      Pages: 658-663

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Heat shock protein 90 inhibitor geldanamycin and 17AAG as anti-cancer therapeutic agents2006

    • Author(s)
      Nobuo, Kubota, Yoshitaka, Matsumoto, Hikaru, Machida
    • Journal Title

      Jpn J Hyperthermic Oncol 22

      Pages: 201-210

    • NAID

      10019596792

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibition of homologous recombination repair inrreadiated tumor cells pretreated with Hsp90 inhibiotr 17-allylamino-17-demethoxygeldanamycin2006

    • Author(s)
      Noguchi, M., Yu, D., Hirayama, R., Ninomiya, Y., Sekine, E., Kubota, N., Ando, K., Okayasu, R
    • Journal Title

      Biochem Biophys Res Commun 351

      Pages: 658-663

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Heat shock protein 90 inhibitor geldanamycin and 17AAG as anti-cancer therapeuticagents.2006

    • Author(s)
      Nobuo Kubota, Yoshitaka Matsumoto, Hikaru Machida
    • Journal Title

      Jpn J Hyperthermic Oncol 22

      Pages: 201-210

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxy-Geldanamycin.2006

    • Author(s)
      Miho Noguchi, Nobuo Kubota, et al.
    • Journal Title

      Biochem Biophys Res Commun 351

      Pages: 658-663

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Heat shock protein 90 inhibitor geldanamycin and 17AAG as anti-cancer therapeutic agents2006

    • Author(s)
      Nobuo Kubota, et al.
    • Journal Title

      Jpn J Hyperthermic Oncol 22(4)

      Pages: 201-210

    • NAID

      10019596792

    • Related Report
      2006 Annual Research Report
  • [Presentation] ヒト腫瘍細胞でのSulforaphaneの放射線増感効果2007

    • Author(s)
      窪田 宜夫, 他
    • Organizer
      第20回日本放射線腫瘍学会
    • Place of Presentation
      福岡
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Radiosensitization by sulforaphane in human Tumor cells2007

    • Author(s)
      Kubota, N., et. al.
    • Organizer
      20th Japanese Society for Therapeutic Radiology and Oncology
    • Place of Presentation
      Fukuoka
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] ヒト腫瘍細胞でのSulforaphaneの放射線増感効果2007

    • Author(s)
      窪田宜夫、他
    • Organizer
      第20回日本放射線腫瘍学会
    • Related Report
      2007 Annual Research Report
  • [Book] 放射線生物学2008

    • Author(s)
      窪田 宜夫
    • Total Pages
      128
    • Publisher
      医療科学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 放射線生物学2008

    • Author(s)
      窪田宜夫
    • Total Pages
      128
    • Publisher
      医療科学社
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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