Roles of nuclear factor-kappa B, 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 i nhibitor. The human p21 promoter harbors p53-responsive elements and an NF- kappaB binding site. We demonstrated, in human breast and colon carcinoma c ells, the binding of NF-kappaB dimers to the kappaB site and the transcript ional activation of the human p21 promoter by daunomycin and by NF-kappaB s ubunits, thereby confirming the functionality of this kappaB binding site. However, using different tumor cell lines where p53 or NF-kappaB was inacti ve, we showed that p21 activation and cell cycle arrest induced by daunomyc in was p53-dependent and NF-kappaB-independent, whereas daunomycin-induced apoptosis was p53- and NF-kappaB-independent.