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

¹ The Wolfson Institute for Biomedical Research, University College London; ² Tumour Biology Laboratory, Cancer Research UK Clinical Centre, Queen Mary's Medical and Dental School at Bart's and the London, London, United Kingdom; and ³ Department of Oral and Maxillofacial Surgery, Queen Alexandra Hospital, Portsmouth, United Kingdom

Requests for reprints: Salvador Moncada, The Wolfson Institute for Biomedical Research, University College London, The Cruciform Building, London WC1E 6BT, United Kingdom. Phone: 44-2076796666; E-mail: s.moncada{at}ucl.ac.uk.

Widespread expression of the -subunit of hypoxia-inducible factor (HIF-1) 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-1 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-1 by a mechanism dependent on free radicals. (Cancer Res 2006; 66(2): 770-4)

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