In vitro effects of nitric oxide synthase inhibitor L-NAME on oral squamous cell carcinoma: a preliminary study

Int J Oral Maxillofac Surg. 2006 Jun;35(6):539-43. doi: 10.1016/j.ijom.2006.01.004. Epub 2006 Feb 23.


It has been reported that increased nitric oxide synthase (NOS) expression and nitric oxide (NO) production may play an important role in cancer biology. The aim of this study was to determine the roles of NO in tumour cellular proliferation and DNA or RNA synthesis, and to investigate the therapeutic potential of NOS inhibitors in oral cancer. After exposure to different concentrations of the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the growth of TSCCa cells, established from a patient with squamous cell carcinoma of the tongue, was evaluated using MTT and crystal violet assay. DNA or RNA synthesis, inducible/endothelial NOS (iNOS/eNOS) mRNA expression and NO production were then examined to determine the possible mechanisms of inhibitory effects of L-NAME on TSCCa cells. L-NAME had an inhibitory effect on TSCCa cell growth in both a concentration- and time-dependent manner. Acridine orange staining revealed that DNA and/or RNA synthesis of TSCCa cells was reduced after treatment with L-NAME. An in situ hybridisation (ISH) study showed clearly that L-NAME down-regulated eNOS and iNOS mRNA expression and this was followed by a decrease in NO production. It is postulated that the NOS/NO pathway may be implicated in cellular proliferation and DNA or RNA synthesis of cancer cells, apart from promoting tumour angiogenesis. Further studies have provided with new insight into the mechanisms by which NOS/NO takes part in oral carcinogenesis, and possible therapeutic interventions based on the NOS/NO pathway for tumour progression control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridine Orange
  • Carcinoma, Squamous Cell / drug therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coloring Agents
  • DNA / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology
  • Enzyme Inhibitors / therapeutic use*
  • Fluorescent Dyes
  • Gentian Violet
  • Humans
  • In Situ Hybridization
  • NG-Nitroarginine Methyl Ester / therapeutic use*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Nitrous Oxide / antagonists & inhibitors
  • RNA / drug effects
  • Tetrazolium Salts
  • Thiazoles
  • Tongue Neoplasms / drug therapy*
  • Tumor Cells, Cultured


  • Coloring Agents
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Tetrazolium Salts
  • Thiazoles
  • Nitric Oxide
  • RNA
  • DNA
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • thiazolyl blue
  • Acridine Orange
  • Gentian Violet
  • Nitrous Oxide
  • NG-Nitroarginine Methyl Ester