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TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.
- Source :
-
Cell death and differentiation [Cell Death Differ] 2003 Jun; Vol. 10 (6), pp. 718-28. - Publication Year :
- 2003
-
Abstract
- Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.
- Subjects :
- Antibodies pharmacology
Apoptosis drug effects
Carcinoma drug therapy
Carcinoma genetics
Caspase 3
Caspases drug effects
Caspases metabolism
Cell Division drug effects
Cell Division physiology
Cell Survival drug effects
Cell Survival physiology
Colonic Neoplasms drug therapy
Colonic Neoplasms genetics
Drug Synergism
Fas Ligand Protein
Humans
Interferon-alpha metabolism
Membrane Glycoproteins antagonists & inhibitors
Membrane Glycoproteins metabolism
Signal Transduction drug effects
Signal Transduction physiology
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha metabolism
Up-Regulation drug effects
Up-Regulation physiology
Apoptosis physiology
Carcinoma metabolism
Colonic Neoplasms metabolism
Interferon-alpha pharmacology
NF-kappa B metabolism
Tumor Necrosis Factor-alpha pharmacology
fas Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1350-9047
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 12761580
- Full Text :
- https://doi.org/10.1038/sj.cdd.4401219