title: NF-κB-associated mechanisms underlying the response of embryonic cells to Doxorubicin.
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.
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@post.tau.ac.il
authors.forename: S
authors.initials: S
authors.lastname: Savion
authors.forename: G
authors.initials: G
authors.lastname: Oserov
authors.forename: H
authors.initials: H
authors.lastname: Orenstein
authors.forename: A
authors.initials: A
authors.lastname: Torchinsky
authors.forename: A
authors.initials: A
authors.lastname: Fein
authors.forename: V
authors.initials: V
authors.lastname: Toder
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D004317:Doxorubicin