NFkappaB activation and drug sensitivity in human neoplastic cells treated with anthracyclines.
NFkappaB (nuclear factor kappaB) is a transcription factor controlling, among others, cell proliferation and apoptosis. The potent activators of NFkappaB are anthracyclines which can activate apoptotic processes. As shown by some authors, NFkappaB activated by these drugs well correlated with their cytotoxic activity. The aim of this study was to assess the effects of doxorubicin (DOX) and its analogs (annamycin, WP903) on the NFkappaB activity in human melanoma cells: a sensitive (ME18) and a resistant to DOX (ME18/R) and its possible correlation with cell sensitivity to these drugs. In the studies, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, ELISA test and confocal microscopy were used. As was shown, DOX, 1.7; 8.6 microM, strongly induced NFkappaB in ME18 cells. Annamycin (ANN), 0.3; 3.0 microM and WP903, 3.0 microM induced NFkappaB in ME18/R cells. PDTC (pyrrolidine dithiocarbamate)--NFkappaB inhibitor made ME18/R cells more sensitive to ANN and WP903 but did not affect cytotoxicity of DOX in ME18 cells. These results suggest that the influence of NFkappaB activation on cytotoxicity of anthracyclines is highly drug- and cell-specific.
Gruber
Beata M
BM
Department of Biochemistry and Biopharmaceuticals, National Medicines Institute, 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
Fokt
Izabela
I
Piebe
Waldemar
W
D018943:Anthracyclines / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D004317:Doxorubicin; C080315:annamycin