Inhibition of rat glioma cell migration and proliferation by a calix[8]arene scaffold exposing multiple GlcNAc and ureido functionalities.
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.
Viola
Santa
S
Department of Experimental and Clinical Pharmacology, University of Catania, Viale Andrea Doria, Catania, Italy.
Consoli
Grazia M L
GM
Merlo
Sara
S
Drago
Filippo
F
Sortino
Maria Angela
MA
Geraci
Corrada
C
D000704:Analysis of Variance; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D047250:Calixarenes / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003517:Cyclopentanes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005910:Glioma / Q000473:pathology*; D017350:N-Acetylgalactosaminyltransferases / Q000378:metabolism*; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014947:Wounds and Injuries / Q000188:drug therapy
C436284:2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; D001562:Benzimidazoles; D003517:Cyclopentanes; D013778:Tetrazolium Salts; D013844:Thiazoles; D047250:Calixarenes; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; C022616:thiazolyl blue; D001973:Bromodeoxyuridine