NF-κb-dependent MnSOD expression protects adenocarcinoma cells from TNF-α-induced apoptosis

Sylvie Delhalle, Valérie Deregowski, Valérie Benoit, Marie Paule Merville, Vincent Bours*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

109 Citations (Scopus)

Abstract

NF-κB is known to exert a cytoprotective action against TNF-α-induced apoptosis. To study the role of NF-κB in various TNF-α-treated epithelial cell lines, we generated stable transfectants overexpressing a mutated unresponsive form of the IκBα inhibitor (MT cells). As NF-κB prevented TNF-α-induced apoptosis in various epithelial cancer cell lines, we searched for NF-κB target gene products responsible for this difference of sensitivity. We observed an increased Bcl-XL expression level in OVCAR-3 cells compared with OVCAR-3 cells expressing a mutated IκBα inhibitor (MT cells). Induction of the antioxidant enzyme MnSOD was detected only in TNF-α-treated OVCAR, MCF7A/Z and HCT116 cells but not in MT cells. Moreover, reactive oxygen species were involved in TNF-α-induced apoptosis, as various antioxidants partially protected these cells from apoptosis. At last, transfection of the MnSOD cDNA in MT cells, which do not express this protein after TNF-α stimulation, partially restored resistance to TNF-α-induced cell death, as observed by clonogenic assays. However, transfection of the Bcl-XL cDNA did not induce any protective effect. Therefore, MnSOD expression is induced by NF-κB in epithelial cancer cells in response to TNF-α, and is at least partially responsible for their resistance to TNF-α-induced apoptosis, presumably through the clearance of death-inducing ROS.

Original languageEnglish
Pages (from-to)3917-3924
Number of pages8
JournalOncogene
Volume21
Issue number24
DOIs
Publication statusPublished - 30 May 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer
  • MnSOD
  • NF-κB
  • TNF-α

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