TY - JOUR
T1 - Constitutive activation of transcription factor NFκB as a possible marker of sensitivity of neoplastic cells to anthracyclines
AU - Gruber, Beata M.
AU - Anuszewska, Elzbieta L.
AU - Bubko, Irena
AU - Kasprzycka-Guttman, Teresa
AU - Misiewicz, Irena
AU - Skupińska, Katarzyna
AU - Priebe, Waldemar
AU - Fokt, Izabela
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2005
Y1 - 2005
N2 - NFκB, 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 NFκB has occurred as pro - apoptotic factor. The potent activators of NFκB are anthracycline anticancer drugs which induce the events of apoptosis. These results could point to the pro - apoptotic role of NFκB. Recent studies have shown that activation of that transcription factor well correlated with cytotoxic activity of anthracyclines. Potential mechanism through which NFκB 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 NFκB 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 NFκB was determined with use of ELISA test and confocal microscopy. As was shown, both methods have occurred as quite comparable. Constitutive activation of NFκB was observed in all neoplastic cells tested independently on sensitivity to anthracyclines. However, these results do not exclude the supportive role of NFκB in apoptotic activity of these drugs. It is necessary to study the influence of the compounds tested here on NFκB activation and on the induction and intensity of apoptotic processes.
AB - NFκB, 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 NFκB has occurred as pro - apoptotic factor. The potent activators of NFκB are anthracycline anticancer drugs which induce the events of apoptosis. These results could point to the pro - apoptotic role of NFκB. Recent studies have shown that activation of that transcription factor well correlated with cytotoxic activity of anthracyclines. Potential mechanism through which NFκB 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 NFκB 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 NFκB was determined with use of ELISA test and confocal microscopy. As was shown, both methods have occurred as quite comparable. Constitutive activation of NFκB was observed in all neoplastic cells tested independently on sensitivity to anthracyclines. However, these results do not exclude the supportive role of NFκB in apoptotic activity of these drugs. It is necessary to study the influence of the compounds tested here on NFκB activation and on the induction and intensity of apoptotic processes.
KW - Anthracyclines
KW - Constitutive activation
KW - Cytotoxicity
KW - NFκB
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M3 - Article
C2 - 16022489
AN - SCOPUS:24944453211
SN - 0001-6837
VL - 62
SP - 17
EP - 23
JO - Acta Poloniae Pharmaceutica - Drug Research
JF - Acta Poloniae Pharmaceutica - Drug Research
IS - 1
ER -