NFκB activation and drug sensitivity in human neoplastic cells treated with anthracyclines

NFκB (nuclear factor κB) is a transcription factor controlling, among others, cell proliferation and apoptosis. The potent activators of NFκB are anthracyclines which can activate apoptotic processes. As shown by some authors, NFκB 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 NFκB 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 μM, strongly induced NFκB in ME18 cells. Annamycin (ANN), 0.3; 3.0 μM and WP903, 3.0 μM induced NFκB in ME18/R cells. PDTC (pyrrolidine dithiocarbamate) - NFκB 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 NFκB activation on cytotoxicity of anthracyclines is highly drug- and cell-specific.