Nitric Oxide Is a Factor in the Stabilization of Hypoxia-Inducible Factor-1α in Cancer: Role of Free Radical Formation

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Abstract
Widespread expression of the α-subunit of hypoxia-inducible factor (HIF-1α) 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-1α was prevented either by inhibition of NOS activity with the nonspecific NOS inhibitor NG-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-1α by a mechanism dependent on free radicals. (Cancer Res 2006; 66(2): 770-4)