Journal
CANCER RESEARCH
Volume 66, Issue 2, Pages 770-774Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-05-0333
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Widespread expression of the alpha-subunit of hypoxia-inducible factor (HIF-1 alpha) 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 alpha, 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 alpha by a mechanism dependent on free radicals.
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