Adriamycin activates NF-κB in human lung carcinoma cells by IκBα degradation

The aim of this study was to investigate the effect of adriamycin (ADR) in signaling activation of NF-kappaB in ADR-sensitive and -resistant GLC(4) human small-cell lung carcinoma. ADR activated NF-kappaB only in ADR-sensitive GLC(4) cells in a time- and dose-dependant manner by stimulating IkappaBalpha degradation after 4 h. Activation of NF-kappaB in response to tumor necrosis factor was intact in both cell lines. Topoisomerase II, a target for a number of chemotherapeutic agents, was depleted in both types of GLC4 cells after ADR treatment, suggesting the stabilization of transient DNA-topoisomerase II complexes. Another transcription factor, Sp1, was activated by ADR, demonstrating the nonspecificity of NF-kappaB activation in ADR-sensitive GLC(4) cells. These findings indicated that resistance to ADR in ADR-sensitive GLC(4) cells did not involve the NF-kappaB transcription factor. (C) 2003 Elsevier Science (USA). All rights reserved.