Constitutive activation of transcription factor NFkappaB as a possible marker of sensitivity of neoplastic cells to anthracyclines.
NFkappaB, a member of the Rel family of transcription factors has been found to be critically important for control of cell proliferation and apoptosis. Although rare, there are systems in which NFkappaB has occurred as pro-apoptotic factor. The potent activators of NFkappaB are anthracycline anticancer drugs which induce the events of apoptosis. These results could point to the pro-apoptotic role of NFkappaB. Recent studies have shown that activation of that transcription factor well correlated with cytotoxic activity of anthracyclines. Potential mechanism through which NFkappaB could play a role in tumorigenesis involves its constitutive activation which was shown in a wide variety of tumour types. The aim of this study was to define the level of activity of NFkappaB in the native human tumour cells differing in sensitivity to anthracycline analogs to study the mechanism responsible for cytotoxic action of these drugs. Constitutive activation of NFkappaB was determined with use of ELISA test and confocal microscopy. As was shown, both methods have occurred as quite comparable. Constitutive activation of NFkappaB was observed in all neoplastic cells tested independently on sensitivity to anthracyclines. However, these results do not exclude the supportive role of NFkappaB in apoptotic activity of these drugs. It is necessary to study the influence of the compounds tested here on NFkappaB activation and on the induction and intensity of apoptotic processes.
Gruber
Beata M
BM
Department of Biochemistry and Biopharmaceuticals, National Institute of Public Health, 30/34 Chełmska Str., 00-725 Warsaw, Poland. b-gruber@il.waw.pl
Anuszewska
Elzbieta L
EL
Bubko
Irena
I
Kasprzycka-Guttman
Teresa
T
Misiewicz
Irena
I
Skupińska
Katarzyna
K
Priebe
Waldemar
W
Fokt
Izabela
I
D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001711:Biotransformation; D002467:Cell Nucleus / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles
D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016328:NF-kappa B; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue