title: Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation.
abstract: 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.
authors.affiliation: The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, London WC1E 6BT, UK.
authors.forename: Marisol
authors.initials: M
authors.lastname: Quintero
authors.forename: Peter A
authors.initials: PA
authors.lastname: Brennan
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Thomas
authors.forename: Salvador
authors.initials: S
authors.lastname: Moncada
mesh_terms: 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
chemical_list: D005609:Free Radicals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase