Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation.
Widespread expression of the alpha-subunit of hypoxia-inducible factor (HIF-1alpha) was observed in samples of human oral squamous cell carcinoma. In all the cases, this was accompanied by a widespread distribution of nitric oxide (NO) synthases (NOS). Furthermore, in three human cell lines derived from human oral squamous cell carcinoma, the accumulation of HIF-1alpha was prevented either by inhibition of NOS activity with the nonspecific NOS inhibitor N(G)-monomethyl-L-arginine or by the antioxidants N-acetyl-L-cysteine and ascorbic acid. We suggest that, in certain forms of cancer, NO might be responsible for the accumulation of HIF-1alpha by a mechanism dependent on free radicals.
Quintero
Marisol
M
The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, London WC1E 6BT, UK.
Brennan
Peter A
PA
Thomas
Gareth J
GJ
Moncada
Salvador
S
D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D005609:Free Radicals; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000502:physiology*; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000503:physiopathology*; D009569:Nitric Oxide / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000502:physiology
D005609:Free Radicals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase