Modulation of NF-kappa B, and Bcl-2 in apoptosis induced by cisplatin in HeLa cells.
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.
Maldonado
V
V
Laboratorio de Biología Molecular, Instituto Nacional de Cancerología, Mexico City, Mexico.
Meléndez-Zajgla
J
J
Ortega
A
A
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*
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