Nitric oxide up-regulates the expression of intercellular adhesion molecule-1 on cancer cells

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 eff ect of NO on the expression of intercellular adhesion molecule-1 (ICAM-1) o n cancer cells. NO donors such as SNP, SNAP and SIN-1 up-regulated the expr ession 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 transcri ptional induction of ICAM-1 mRNA. Up-regulation of ICAM-1 mBNA by NO donors was inhibited by carboxy-PTIO, a NO scavenger. Although NF-kappa B activit y was induced by NO donors, AP-1 was not induced by them. Staurosporin, a p rotein kinase C (PKC) inhibitor, inhibited the induction of ICAM-1 on NA ce lls by NO, whereas genistein, a protein tyrosine kinase inhibitor, did not. These findings indicate that NO up-regulates ICAM-1 expression on cancer c ells by a regulatory mechanism involving PKC and suggest that NF-kappa B, b ut not AP-1, might be involved in induction of ICAM-1 by NO in cancer cells . (C) 1999 Academic Press.