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

Biochem Biophys Res Commun. 1999 Apr 13;257(2):395-9. doi: 10.1006/bbrc.1999.0476.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoates / pharmacology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion Molecules / metabolism
  • Free Radical Scavengers / pharmacology
  • Genistein / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Molsidomine / analogs & derivatives
  • Molsidomine / pharmacology
  • NF-kappa B / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Donors / pharmacology
  • Nitroprusside / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • RNA, Messenger / metabolism
  • S-Nitroso-N-Acetylpenicillamine
  • Staurosporine / pharmacology
  • Tongue Neoplasms
  • Transcription Factor AP-1 / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects*

Substances

  • Benzoates
  • Cell Adhesion Molecules
  • Free Radical Scavengers
  • Imidazoles
  • NF-kappa B
  • Nitric Oxide Donors
  • RNA, Messenger
  • Transcription Factor AP-1
  • Intercellular Adhesion Molecule-1
  • 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
  • Nitroprusside
  • Nitric Oxide
  • linsidomine
  • S-Nitroso-N-Acetylpenicillamine
  • Molsidomine
  • Genistein
  • Protein Kinase C
  • Penicillamine
  • Staurosporine