Adriamycin activates NF-kappaB in human lung carcinoma cells by IkappaBalpha degradation.

Abstract

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.

• Authors: Maud Andriollo, Alain Favier, Pascale Guiraud
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 413 Issue 1 Pg. 75-82 (May 01 2003) ISSN: 0003-9861 [Print] United States
• PMID: 12706343 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• DNA-Binding Proteins
• I-kappa B Proteins
• NF-kappa B
• NFKBIA protein, human
• NF-KappaB Inhibitor alpha
• Doxorubicin
• DNA
• CASP3 protein, human
• Caspase 3
• Caspases
• DNA Topoisomerases, Type II

Topics

• Antigens, Neoplasm
• Antineoplastic Agents (pharmacology)
• Base Sequence
• Carcinoma, Small Cell (drug therapy, genetics, metabolism)
• Caspase 3
• Caspases (metabolism)
• DNA (genetics)
• DNA Topoisomerases, Type II (metabolism)
• DNA-Binding Proteins
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm
• Humans
• I-kappa B Proteins (metabolism)
• Lung Neoplasms (drug therapy, genetics, metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (genetics, metabolism)
• Signal Transduction (drug effects)
• Tumor Cells, Cultured