1-3-dihydroxy-4-4-5-5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole and Carcinoma--Squamous-Cell

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.

Topics: Benzoates; Carcinoma, Squamous Cell; Cell Adhesion Molecules; Free Radical Scavengers; Genistein; Humans; Imidazoles; Intercellular Adhesion Molecule-1; Molsidomine; NF-kappa B; Nitric Oxide; Nitric Oxide Donors; Nitroprusside; Penicillamine; Phosphorylation; Promoter Regions, Genetic; Protein Kinase C; RNA, Messenger; S-Nitroso-N-Acetylpenicillamine; Staurosporine; Tongue Neoplasms; Transcription Factor AP-1; Tumor Cells, Cultured; Up-Regulation