NF-kappaB inhibition impairs the radioresponse of hypoxic EMT-6 tumour cells through downregulation of inducible nitric oxide synthase.
Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB). Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsine oxide and lactacystin. Contrasting to other studies, our data show that inhibition of NF-kappaB may impair the radioresponse of tumour cells through downregulation of iNOS.
De Ridder
M
M
Oncology Center, Cancer Research Unit, Academic Hospital Free University Brussels (A.Z.-V.U.B.), Laarbeeklaan 101, B 1090, Brussels, Belgium. Mark.De.Ridder@vub.ac.be
Van den Berge
D L
DL
Verovski
V N
VN
Monsaert
C
C
Wauters
N
N
Storme
G A
GA
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001152:Arsenicals / Q000494:pharmacology; D015687:Cell Hypoxia; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015536:Down-Regulation; D007769:Lactams; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D001152:Arsenicals; D007769:Lactams; D009097:Multienzyme Complexes; D016328:NF-kappa B; C029341:oxophenylarsine; C067713:lactacystin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D010100:Oxygen; D000111:Acetylcysteine