Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1α in cancer:: Role of free radical formation

Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1α in cancer:: Role of free radical formation
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DOI:
10.1158/0008-5472.can-05-0333
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发表时间:
2006-01-15
期刊:
影响因子:
11.2
通讯作者:
Moncada, S
Moncada, S
中科院分区:
医学1区
文献类型:
--
作者:
Quintero, M;Brennan, PA;Moncada, S

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缺氧诱导因子α亚基(HIF-1 α)在人口腔鳞状细胞癌中广泛表达。在所有病例中,这都伴随着一氧化氮(NO)合成酶(NOS)的广泛分布。此外,在来自人类口腔鳞状细胞癌的三种人类细胞系中,通过非特异性NOS抑制剂n - g -单甲基- l-精氨酸或抗氧化剂n -乙酰- l-半胱氨酸和抗坏血酸抑制NOS活性,可以阻止HIF-1 α的积累。我们认为,在某些形式的癌症中,NO可能通过依赖于自由基的机制负责HIF-1 α的积累。
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.