Cell death in NF-kappaB-dependent tumour cell lines as a result of NF-kappaB trapping by linker-modified hairpin decoy oligonucleotide.
The transcription factor NF-kappaB is frequently activated in cancer, and is therefore a valuable target for cancer therapy. Decoy oligodeoxynucleotides (ODNs) inhibit NF-kappaB by preventing its binding to the promoter region of target genes. Few studies have used NF-kappaB-targeting with ODNs in cancer. Using a hairpin NF-kappaB-decoy ODN we found that it induced growth inhibition and cell death in NF-kappaB-dependent tumour cell lines. The ODN colocalized with the p50 subunit of NF-kappaB in cells and directly interacted with it in nuclear extracts. In TNFalpha-treated cells the ODN and the p50 subunit were found in the cytoplasm suggesting that the complex did not translocate to the nucleus. Transcriptional activity of NF-kappaB was efficiently inhibited by the ODN, whereas a scrambled ODN was without effect on transcription. Thus, ODN-mediated inhibition of NF-kappaB can efficiently promote cell death in cancer cells providing a potentially powerful approach to tumour growth inhibition.
Laguillier
Christelle
C
Université Paris 13, EA3406, France.
Hbibi
Ali Tadlaoui
AT
Baran-Marszak
Fanny
F
Metelev
Valeri
V
Cao
An
A
Cymbalista
Florence
F
Bogdanov
Alexei
A
Fagard
Remi
R
D001665:Binding Sites; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000473:pathology*; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C468119:NF-kappaB decoy; C489548:NFKB1 protein, human; D009838:Oligodeoxyribonucleotides