2001 Fiscal Year Final Research Report Summary
NF-κ B mediated apoptosis induced by TNF/IFN-α
| Project/Area Number |
12671228
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Okayama University Hospital |
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Principal Investigator |
HAISA Minoru Okayama University Hospital, assistant, 医学部附属病院, 助手 (70322229)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | cytokine cross-talk / apoptosis / NF-κB / TNF / IFN-α / Fas |
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| 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.
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Research Products
(2 results)
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[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)
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