Inhibition of rat glioma cell migration and proliferation by a calix[8]arene scaffold exposing multiple GlcNAc and ureido functionalities

J Neurochem. 2008 Nov;107(4):1047-55. doi: 10.1111/j.1471-4159.2008.05656.x. Epub 2008 Sep 6.

Abstract

Beta1,4-Galactosyltransferases (beta1,4-GalTase) exposed on the cell surface are involved in cell migration. Specifically, beta1,4-GalTase V is highly expressed in glioma and promotes invasion, growth, and survival of glioma cells. A glycocalix[8]arene exposing N-acetylglucosamine (GlcNAc) residues (compound 1) inhibited rat C6 glioma cell migration as assessed in a scratch wound model. This effect was related to inhibition of focal adhesion kinase phosphorylation, measured by western blot analysis, and specifically observed in the area bordering the scratch wound. Compound 1 inhibited also C6 cell proliferation, an effect unrelated to its ability to interact with GalTase as it was mimicked by different calix[8]arene derivatives, all characterized by multivalency and ureido groups. Compound 1 did not induce apoptotic death, but caused a different distribution of C6 cells within the cell cycle. The results here reported identify compound 1 as a molecule able to exert inhibitory effects on C6 cell migration and proliferation, independently, because of distinct components in its structure.

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzimidazoles / pharmacology
  • Bromodeoxyuridine / metabolism
  • Calixarenes / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cyclopentanes / pharmacology
  • Enzyme Activation / drug effects
  • Focal Adhesion Kinase 1 / metabolism
  • Glioma / pathology*
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Rats
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors
  • Wounds and Injuries / drug therapy

Substances

  • 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole
  • Benzimidazoles
  • Cyclopentanes
  • Tetrazolium Salts
  • Thiazoles
  • Calixarenes
  • N-Acetylgalactosaminyltransferases
  • (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
  • Focal Adhesion Kinase 1
  • Ptk2 protein, rat
  • thiazolyl blue
  • Bromodeoxyuridine