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IFNalpha sensitizes ME-180 human cervical cancer cells to TNFalpha-induced apoptosis by inhibiting cytoprotective NF-kappaB activation.

Authors
 Kyoungho Suk  ;  Yun-Hee Kim  ;  Inik Chang  ;  Ja Young Kim  ;  Yun-Hee Choi  ;  Kye Young Lee  ;  Myung-Shik Lee 
Citation
 FEBS Letters, Vol.495(1-2) : 66-70, 2001 
Journal Title
 FEBS Letters 
ISSN
 0014-5793 
Issue Date
2001
Abstract
Tumor necrosis factor alpha (TNFalpha) induces apoptosis of a variety of tumor cell types. The anti-tumor effect of TNFalpha is often augmented by interferon (IFN) gamma. We hypothesized that IFNalpha, which shares many biological activities with IFNgamma, might also synergize with TNFalpha for the induction of tumor cell death. We tested our hypothesis using ME-180 human cervical cancer cells exposed to either IFNalpha or TNFalpha alone or both. We analyzed the death of ME-180 cells by biochemical and cytological means, and investigated the molecular mechanism underlying cytotoxic synergism between the two cytokines. We found that (i) IFNalpha/TNFalpha synergistically induced apoptosis of ME-180 cells, which was accompanied by activation of caspases-3 and -8; (ii) IFNalpha induced signal transducer and activator of transcription (STAT) 1 phosphorylation, and transfection of phosphorylation-defective STAT1 dominant-negative mutant inhibited IFNalpha/TNFalpha-induced apoptosis; (iii) inhibition of nuclear factor kappaB (NF-kappaB) by proteasome inhibitor MG-132 sensitized ME-180 cells to TNFalpha alone; (iv) IFNalpha treatment attenuated TNFalpha-induced NF-kappaB reporter activity, while it did not inhibit DNA binding of NF-kappaB. Taken collectively, our results indicate that IFNalpha sensitizes ME-180 cells to TNFalpha-induced apoptosis by inhibiting TNFalpha-mediated cytoprotective NF-kappaB activation, and this sensitizing effect of IFNalpha is mediated through a STAT1-dependent pathway.
Full Text
http://onlinelibrary.wiley.com/doi/10.1016/S0014-5793(01)02335-3/epdf
DOI
10.1016/S0014-5793(01)02335-3
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
장인익(Chang, In Ik)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143240
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