Inhibitory effects of nitric oxide on invasion of human cancer cells

Hypoxia increased the ability of two human cancer cell lines, PC-3M and T24, to invade through Matrigel, while sodium nitroprusside (SNP), a nitric oxide (NO) donor, strongly inhibited this invasion, along with down-regulating HIF-1α. SNP also inhibited the function of mitochondria in PC-3M cells, and mitochondrion-specific inhibitors reduced the invasion of these cells. Furthermore, knocking down either Rieske iron–sulfur protein (Fe–S) of mitochondrial complex III or HIF-1β in these cells decreased their invasive potential. Our findings suggest that NO inhibits invasion of cancer cells via both inhibition of HIF-1, and impairment of mitochondria.