Abstract
Nitric oxide (NO) is an unstable free radical that functions as a cytotoxic agent secreted by macrophages to kill cancer cells. Here we report the effect of NO on the expression of intercellular adhesion molecule-1 (ICAM-1) on cancer cells. NO donors such as SNP, SNAP and SIN-1 up-regulated the expression of ICAM-1 on NA cells, a squamous cell carcinoma cell line. Northern blot analysis showed that the induction of ICAM-1 might be due to transcriptional induction of ICAM-1 mRNA. Up-regulation of ICAM-1 mRNA by NO donors was inhibited by carboxy-PTIO, a NO scavenger. Although NF-kappaB activity was induced by NO donors, AP-1 was not induced by them. Staurosporin, a protein kinase C (PKC) inhibitor, inhibited the induction of ICAM-1 on NA cells by NO, whereas genistein, a protein tyrosine kinase inhibitor, did not. These findings indicate that NO up-regulates ICAM-1 expression on cancer cells by a regulatory mechanism involving PKC and suggest that NF-kappaB, but not AP-1, might be involved in induction of ICAM-1 by NO in cancer cells.
Copyright 1999 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Benzoates / pharmacology
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Adhesion Molecules / metabolism
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Free Radical Scavengers / pharmacology
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Genistein / pharmacology
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Humans
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Imidazoles / pharmacology
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism*
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Molsidomine / analogs & derivatives
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Molsidomine / pharmacology
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NF-kappa B / metabolism
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / metabolism
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Nitric Oxide / pharmacology*
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Nitric Oxide Donors / pharmacology
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Nitroprusside / pharmacology
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Penicillamine / analogs & derivatives
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Penicillamine / pharmacology
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Phosphorylation / drug effects
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Promoter Regions, Genetic / genetics
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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RNA, Messenger / metabolism
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S-Nitroso-N-Acetylpenicillamine
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Staurosporine / pharmacology
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Tongue Neoplasms
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Transcription Factor AP-1 / metabolism
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Tumor Cells, Cultured
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Up-Regulation / drug effects*
Substances
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Benzoates
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Cell Adhesion Molecules
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Free Radical Scavengers
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Imidazoles
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NF-kappa B
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Nitric Oxide Donors
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RNA, Messenger
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Transcription Factor AP-1
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Intercellular Adhesion Molecule-1
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1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
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Nitroprusside
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Nitric Oxide
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linsidomine
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S-Nitroso-N-Acetylpenicillamine
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Molsidomine
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Genistein
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Protein Kinase C
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Penicillamine
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Staurosporine