Abstract
Background: DMXAA (5,6-dimethylxanthenone-4-acetic acid; AS1404), a vascular disrupting agent currently in clinical trials, induces tumour endothelial cell apoptosis in vivo in mice and in cancer patients. DMXAA activates NF-κB in many different cell types. In this study, whether DMXAA-induced endothelial cell apoptosis was NF-κB dependent was determined. Materials and Methods: HUVEC endothelial and T24 endothelial-like cells were treated with DMXAA and apoptosis was measured by terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL). NF-κB activation was measured by electrophoretic mobility shift assays (EMSA). T24 cells were transfected with IκBαM, a mutant form of the IκBα gene which cannot be phosphorylated and degraded, hence preventing NF-κB expression. Results: No NF-κB up-regulation was detected in apoptotic HUVEC treated with DMXAA. The IκBαM-transfected T24 cells showed similar apoptotic responses to those of parental cells. Conclusion: The DMXAA-induced apoptosis is neither mediated by, nor inhibited by, the expression of the NF-κB pathway.
- Received October 6, 2006.
- Accepted November 23, 2006.
- Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved