title: Modulation of NF-kappa B, and Bcl-2 in apoptosis induced by cisplatin in HeLa cells.
abstract: Cisplatin exposure induces apoptosis in HeLa cells. Since the interaction of this drug with DNA produces reactive oxygen species, we performed an analysis of the oxidative stress-responsive factors AP-1 and NF-kappa B. Although AP-1 levels were not modified during cisplatin exposure, electrophoretic mobility shift assays demonstrated an increase in NF-kappa B DNA binding activity that correlated with a decrease of the inhibitory protein I kappa B alpha and a specific relocalization of c-Rel, as assessed by immunoblotting and immunofluorescence. No changes in the levels or localization of p65 were found. Interestingly, I kappa B alpha relocalized to the nucleus, probably in order to regulate the binding of specific complexes. This process was accompanied by a decrease of the antiapoptotic protein Bcl-2, and a relocalization of p53 protein to the nucleus. Since HeLa cells lost most of their p53 protein due to a specific E6-dependent degradation, cisplatin could be inhibiting this degradation, since the p53 total levels were not increased during the exposure to the drug.
authors.affiliation: Laboratorio de Biología Molecular, Instituto Nacional de Cancerología, Mexico City, Mexico.
authors.forename: V
authors.initials: V
authors.lastname: Maldonado
authors.forename: J
authors.initials: J
authors.lastname: Meléndez-Zajgla
authors.forename: A
authors.initials: A
authors.lastname: Ortega
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002945:Cisplatin / Q000494:pharmacology*; D004586:Electrophoresis; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020569:Proto-Oncogene Proteins c-rel; C497593:RELB protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051841:Transcription Factor RelB; D002945:Cisplatin