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Published on: January 7, 2019

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

S Savion1, G Oserov, H Orenstein

  • 1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@post.tau.ac.il

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|January 1, 2013
PubMed

Insights

The p65 subunit of Nuclear Factor kappa B (NF-κB) plays a crucial role in how embryonic cells respond to the chemotherapy drug Doxorubicin (DOX). Its absence increases cell death and apoptosis, highlighting its importance in teratogen response.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Toxicology

Background:

  • The role of Nuclear Factor kappa B (NF-κB) in teratogen-induced apoptosis remains unclear.
  • The p65 subunit is a key component of the NF-κB pathway.

Purpose of the Study:

  • To investigate the involvement of the NF-κB p65 subunit in the embryonic cellular response to Doxorubicin (DOX).
  • To determine if the p65 subunit influences apoptosis and cell cycle arrest induced by the teratogen DOX.

Main Methods:

  • Comparison of Doxorubicin (DOX) effects on wild-type (WT) and p65 knockout (p65(-/-)) mouse embryonic fibroblasts (MEFs).
  • Assessment of cell survival, proliferation, apoptosis, and cell cycle distribution (G2/M arrest).
  • Analysis of apoptosis-associated protein expression (p65, p53, IκBα, bcl-2).

Main Results:

  • p65(-/-) MEFs exhibited significantly reduced cell survival, proliferation, and increased apoptosis compared to WT MEFs upon DOX exposure.
  • DOX induced a more prominent G2/M cell cycle arrest in WT MEFs than in p65(-/-) MEFs.
  • Differential expression of p53, IκBα, and bcl-2 was observed between WT and p65(-/-) MEFs treated with DOX.

Conclusions:

  • The embryonic cellular response to the teratogen Doxorubicin (DOX) is dependent on the NF-κB p65 subunit.
  • The p65 subunit plays a protective role against DOX-induced apoptosis in embryonic cells.
  • These findings implicate NF-κB p65 in regulating embryonic sensitivity to teratogenic agents.

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