NF-κB-associated mechanisms underlying the response of embryonic cells to Doxorubicin

S. Savion, G. Oserov, H. Orenstein, A. Torchinsky, A. Fein, V. Toder

Research output: Contribution to journalArticlepeer-review

Abstract

The involvement of NF-κB in the regulation of teratogen-induced apoptosis has not been established yet. Therefore, we tried to assess the involvement of the p65 subunit of NF-κB in the embryonic response to the anti-cancer drug Doxorubicin (DOX). Thus, exposure of p65 knockout (p65-/-) or wild type (WT) mouse embryonic fibroblasts (MEFs) to DOX resulted in a decrease in cell survival, culture density and cell proliferation, which was found to be more prominent in p65-/- MEFs. Those phenomena were accompanied by a DOX-induced increase in the proportion of apoptotic cells, which was demonstrated only in p65-/- cells and a G2/M arrest, which was found to be more prominent in WT cells. Furthermore, DOX-treated WT and p65-/- MEFs differed in their expression of various apoptosis-associated molecules, when the former demonstrated a decrease in the percentage of p65-positive and a more prominent decrease in the percentage of p53-positive cells, while a decreased percentage of IκBα-positive and a more prominent decrease in the percentage of bcl-2-positive cells was detected among the latter. The fact that the response of the cells to the teratogen was clearly p65-dependent implicates this molecule to be involved in the response of the embryonic cells to DOX.

Original languageEnglish
Pages (from-to)804-811
Number of pages8
JournalToxicology in Vitro
Volume27
Issue number2
DOIs
StatePublished - Mar 2013

Keywords

  • Apoptosis
  • Cell cycle
  • Doxorubicin
  • MEFs
  • NF-κB
  • P65

Fingerprint

Dive into the research topics of 'NF-κB-associated mechanisms underlying the response of embryonic cells to Doxorubicin'. Together they form a unique fingerprint.

Cite this