Abstract
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-1alpha. 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-1beta 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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Antimycin A / pharmacology
-
Cell Hypoxia
-
Cell Line, Tumor
-
Cell Movement / drug effects*
-
Cell Proliferation / drug effects
-
Electron Transport Complex III / genetics
-
Electron Transport Complex III / metabolism
-
Humans
-
Hypoxia-Inducible Factor 1 / genetics
-
Hypoxia-Inducible Factor 1 / metabolism
-
Immunoblotting
-
Iron-Sulfur Proteins / genetics
-
Iron-Sulfur Proteins / metabolism
-
Methacrylates / pharmacology
-
Mitochondria / drug effects
-
Mitochondria / metabolism
-
Neoplasm Invasiveness
-
Neoplasms / genetics
-
Neoplasms / metabolism
-
Neoplasms / pathology
-
Nitric Oxide / metabolism*
-
Nitric Oxide Donors / pharmacology*
-
Nitroprusside / pharmacology*
-
Oligomycins / pharmacology
-
RNA Interference
-
RNA, Small Interfering / genetics
-
Thiazoles / pharmacology
-
Transfection
-
Uncoupling Agents / pharmacology
Substances
-
Hypoxia-Inducible Factor 1
-
Iron-Sulfur Proteins
-
Methacrylates
-
Nitric Oxide Donors
-
Oligomycins
-
RNA, Small Interfering
-
Rieske iron-sulfur protein
-
Thiazoles
-
Uncoupling Agents
-
Nitroprusside
-
Nitric Oxide
-
Antimycin A
-
myxothiazol
-
Electron Transport Complex III