title: NF-kappaB-independent induction of endothelial cell apoptosis by the vascular disrupting agent DMXAA.
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-kappaB in many different cell types. In this study, whether DMXAA-induced endothelial cell apoptosis was NF-kappaB dependent was determined.
  
  
  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-kappaB activation was measured by electrophoretic mobility shift assays (EMSA). T24 cells were transfected with IkappaBalphaM, a mutant form of the IkappaBalpha gene which cannot be phosphorylated and degraded, hence preventing NF-kappaB expression.
  
  
  RESULTS
  No NF-kappaB up-regulation was detected in apoptotic HUVEC treated with DMXAA. The IkappaBalphaM-transfected T24 cells showed similar apoptotic responses to those of parental cells.
  
  
  CONCLUSIONS
  The DMXAA-induced apoptosis is neither mediated by, nor inhibited by, the expression of the NF-kappaB pathway.
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: See-Tarn
authors.initials: ST
authors.lastname: Woon
authors.forename: Sandy S C
authors.initials: SS
authors.lastname: Hung
authors.forename: Derek C F
authors.initials: DC
authors.lastname: Wu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Schooltink
authors.forename: Rachel
authors.initials: R
authors.lastname: Sutherland
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Chamley
authors.forename: Lai-Ming
authors.initials: LM
authors.lastname: Ching
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D014162:Transfection; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D044004:Xanthones; C066668:vadimezan; D000072000:NF-KappaB Inhibitor alpha