TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells

Cell Death Differ. 2003 Jun;10(6):718-28. doi: 10.1038/sj.cdd.4401219.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Carcinoma / drug therapy
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • 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
  • Colonic Neoplasms / metabolism*
  • Drug Synergism
  • Fas Ligand Protein
  • Humans
  • Interferon-alpha / metabolism
  • Interferon-alpha / pharmacology*
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • NF-kappa B / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • fas Receptor / metabolism*

Substances

  • Antibodies
  • FASLG protein, human
  • Fas Ligand Protein
  • Interferon-alpha
  • Membrane Glycoproteins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • CASP3 protein, human
  • Caspase 3
  • Caspases