Glycine as a potent anti-angiogenic nutrient for tumor growth

J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S62-4. doi: 10.1111/j.1440-1746.2006.04655.x.

Abstract

Accumulating lines of evidence suggest a possibility that glycine is useful as an immuno-modulating amino acid. Glycine most likely prevents the lipopolysaccharide (LPS)-induced elevation of intracellular Ca(2+) concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Moreover, it was reported that dietary glycine inhibits the growth of tumors. Vascular endothelial growth factor (VEGF) plays a critical role in cancer progression by promoting new blood vessel formation. Activation of VEGF receptor has been shown to result in activation of phospholipase C-gamma and increases in intracellular Ca(2+) concentration. The VEGF-induced cell proliferation is dependent on intracellular Ca(2+) concentration. The effects of glycine on VEGF-induced increases in intracellular Ca(2+) concentration in endothelial cell line (CPA) were studied. The VEGF increased intracellular Ca(2+) concentration rapidly, but glycine blunted increases in intracellular Ca(2+) concentration due to VEGF. Further, the inhibitory effects of glycine were prevented by low concentrations of strychnine (1 micromol/L) or incubation with chloride-free buffer. Moreover, glycine increased influx of radiolabeled chloride into CPA cells approximately 10-fold. Furthermore, mRNA 92% identical to the beta-subunit of the glycine-gated chloride channel from spinal cord was identified in endothelial cells using reverse transcription-polymerase chain reaction. Finally, glycine significantly diminished serum-stimulated proliferation and migration of endothelial cells. These data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated chloride channel. This hyperpolarizes the cell membrane and blocks influx of Ca(2+), thereby minimizing growth factor-mediated signaling. Therefore, glycine can be used not only for treatment of inflammation, but also for chemoprevention and treatment of carcinoma.

MeSH terms

  • Calcium / metabolism
  • Cell Movement / drug effects
  • Chloride Channels / drug effects
  • Endothelium, Vascular / drug effects
  • Glycine / pharmacology*
  • Humans
  • In Vitro Techniques
  • Kupffer Cells / drug effects*
  • Melanoma / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Skin Neoplasms / drug therapy*
  • Strychnine / pharmacology
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / physiology

Substances

  • Chloride Channels
  • Vascular Endothelial Growth Factor A
  • Strychnine
  • Calcium
  • Glycine