skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways

Abstract

Blockage of either nuclear factor-{kappa}B (NF-{kappa}B) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-{kappa}B activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-{kappa}B. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-{kappa}B activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-{kappa}B activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-{kappa}B and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-{kappa}B and Akt, which may be applied in lung cancer therapy.

Authors:
 [1];  [1];  [2]
  1. Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States)
  2. Molecular Biology and Lung Cancer Program, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, NM 87108 (United States). E-mail: ylin@lrri.org
Publication Date:
OSTI Identifier:
20979877
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2007.02.030; PII: S0006-291X(07)00313-0; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; APOPTOSIS; CARCINOMAS; INHIBITION; LUNGS; PHOSPHORYLATION; THERAPY; TOXICITY

Citation Formats

Wang Xia, Chen Wenshu, and Lin Yong. Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.02.030.
Wang Xia, Chen Wenshu, & Lin Yong. Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways. United States. doi:10.1016/j.bbrc.2007.02.030.
Wang Xia, Chen Wenshu, and Lin Yong. Fri . "Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways". United States. doi:10.1016/j.bbrc.2007.02.030.
@article{osti_20979877,
title = {Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways},
author = {Wang Xia and Chen Wenshu and Lin Yong},
abstractNote = {Blockage of either nuclear factor-{kappa}B (NF-{kappa}B) or Akt sensitizes cancer cells to TNF-induced apoptosis. In this study, we investigated the undetermined effect of concurrent blockage of these two survival pathways on TNF-induced cytotoxicity in lung cancer cells. The results show that Akt contributes to TNF-induced NF-{kappa}B activation in lung cancer cells through regulating phosphorylation of the p65/RelA subunit of NF-{kappa}B. Although individually blocking IKK or Akt partially suppressed TNF-induced NF-{kappa}B activation, concurrent suppression of these pathways completely inhibited TNF-induced NF-{kappa}B activation and downstream anti-apoptotic gene expression, and synergistically potentiated TNF-induced cytotoxicity. Moreover, suppression of Akt inhibited the Akt-mediated anti-apoptotic pathway through dephosphorylation of BAD. These results indicate that concurrent suppression of NF-{kappa}B and Akt synergistically sensitizes TNF-induced cytotoxicity through blockage of distinct survival pathways downstream of NF-{kappa}B and Akt, which may be applied in lung cancer therapy.},
doi = {10.1016/j.bbrc.2007.02.030},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 355,
place = {United States},
year = {Fri Apr 13 00:00:00 EDT 2007},
month = {Fri Apr 13 00:00:00 EDT 2007}
}