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

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.

• Authors: Santa Viola, Grazia M L Consoli, Sara Merlo, Filippo Drago, Maria Angela Sortino, Corrada Geraci
• Journal: Journal of neurochemistry (J Neurochem) Vol. 107 Issue 4 Pg. 1047-55 (Nov 2008) ISSN: 1471-4159 [Electronic] England
• PMID: 18778307 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• 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)