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NF-κ B mediated apoptosis induced by TNF/IFN-α

Research Project

Project/Area Number 12671228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOkayama University Hospital

Principal Investigator

HAISA Minoru  Okayama University Hospital, assistant, 医学部附属病院, 助手 (70322229)

Co-Investigator(Kenkyū-buntansha) TANAKA Noriaki  Okayama University Graduate School of Medicine and Denistry, Professor, 大学院・医歯学総合研究科, 教授 (10127566)
NAOMOTO Yoshio  Okayama University Graduate School of Medicine and Denistry, Associate, 大学院・医歯学総合研究科, 助教授 (00237190)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordscytokine cross-talk / apoptosis / NF-κB / TNF / IFN-α / Fas / NF-kB / TNF-α
Research Abstract

Recently, we reported that TNF/IFN-α combined treatment inhibited the in vitro and in vivo proliferation of human colon adenocarcinoma cells. Immunostaining and EMSA revealed that NF-κB was activated strongly by TNF/IFN-α compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-κB, by using a NF-κB decoy, reduced cell viability after treatment with TNF only, NF-κB decoy resulted in recovery of cell viability after TNF/IFN-α treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-α, while suppression of caspase-3 activity was observed in cells transfected with NF-κB decoy and then treated by TNF/IFN-α. On the other hand, Fas expression was strongly enhanced by TNF/IFN-α, and inhibition of TNF/IFN-α-induced NF-κB activation, by using NF-κB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-α and anti-FasL antibody. Taken together, our findings suggest that activated NF-κB induced by the cross-talk between TNF and IFN-α is a novel pro-apoptotic signal acting via enhancement of Fas expression. Our observations provide the first evidence in carcinoma cells indicating that TNF-induced NF-κB activation, which has an anti-apoptotic function, may be modified to a pro-apoptotic function by cytokine cross-talk between TNF and IFN-α. Such actions might be of clinicopharmacological value, where apoptosis of tumor cells could be efficiently induced by TNF/IFN-α and FasL, or up-regulators of FasL in combination might become a clinically applicable new strategy in cancer therapy.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Kimura M, Haisa M, et al.: "TNF combined with IFN-α accelerates NF-κB-mediated apoptosis through enhancement of Fas expression in colon cancer cells"Cell Death and Differentiation. 10. 718-738 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kimura M, Haisa M, Ueteuka H, Takaoka M, Ohkawa T, Kawashima R, Yamatsuji T, Gunduz M, Kaneda Y, Tanaka N, and Naomoto Y.: "TNF combined wilhIFN-α accelerates NF-κB-mediated apoplosis through enhancement of Fas expression in colon cancer cells"Cell Death and Differentiation. 10(6). 718-728 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary

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Published: 2000-04-01   Modified: 2016-04-21  

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