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-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.
Wang
Feng
F
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
Zhang
Ruixue
R
Xia
Tian
T
Hsu
Erin
E
Cai
Ying
Y
Gu
Zhennan
Z
Hankinson
Oliver
O
D000968:Antimycin A / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009840:Oligomycins / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology; D014162:Transfection; D014475:Uncoupling Agents / Q000494:pharmacology
D051793:Hypoxia-Inducible Factor 1; D007506:Iron-Sulfur Proteins; D008689:Methacrylates; D020030:Nitric Oxide Donors; D009840:Oligomycins; D034741:RNA, Small Interfering; C037989:Rieske iron-sulfur protein; D013844:Thiazoles; D014475:Uncoupling Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000968:Antimycin A; C030517:myxothiazol; D014450:Electron Transport Complex III