Roles of nuclear factor-kappaB, p53, and p21/WAF1 in daunomycin-induced cell cycle arrest and apoptosis.
Daunomycin is a potent inducer of p53 and NF-kappaB transcription factors. It is also able to increase the amount of the p21 cyclin-dependent kinase inhibitor. The human p21 promoter harbors p53-responsive elements and an NF-kappaB binding site. We demonstrated, in human breast and colon carcinoma cells, the binding of NF-kappaB dimers to the kappaB site and the transcriptional activation of the human p21 promoter by daunomycin and by NF-kappaB subunits, thereby confirming the functionality of this kappaB binding site. However, using different tumor cell lines where p53 or NF-kappaB was inactive, we showed that p21 activation and cell cycle arrest induced by daunomycin was p53-dependent and NF-kappaB-independent, whereas daunomycin-induced apoptosis was p53- and NF-kappaB-independent.
Hellin
A C
AC
Laboratory of Medical Chemistry and Medical Oncology, University of Liège, Sart-Tilman, Liège, Belgium.
Bentires-Alj
M
M
Verlaet
M
M
Benoit
V
V
Gielen
J
J
Bours
V
V
Merville
M P
MP
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D003630:Daunorubicin / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D003630:Daunorubicin