Adriamycin activates NF-kappaB in human lung carcinoma cells by IkappaBalpha 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 4h. 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 GLC(4) 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.
Andriollo
Maud
M
Laboratoire de Biologie du Stress Oxydant, MNERT JE538 CEA LRC 8M, Faculté de Pharmacie, Université Joseph Fourier, Grenoble, France. Maud.Andriollo@ujf-grenoble.fr
Favier
Alain
A
Guiraud
Pascale
P
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha; D004317:Doxorubicin; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D004250:DNA Topoisomerases, Type II