Modulation of C6 Glioma Cell Proliferation by Ureido-Calix[8]arenes.
Calixarenes are synthetic macrocyclic compounds that may serve as scaffolds for biologically active molecules and have been proposed as potential anticancer agents. We synthesized a ureido-calix[8]arene carrying N-acetyl-D-glucosamine residue (compound 1) and had previously demonstrated that it inhibits C6 glioma cell migration and proliferation, with divergent mechanisms. In the present work we explored in more detail the antiproliferative effect of compound 1, comparing it to related compounds lacking either the sugar moieties (compound 2), the multiple ureido groups (compound 3) or both (compound 4). The results show that the action of compound 1 is independent of the N-acetyl-D-glucosamine residues, requires the presence of multiple ureido groups and does not seem to involve focal adhesion kinase signaling. Inhibition of proliferation is reduced by preincubation with epidermal growth factor (EGF) and vascular endothelial growth factor (20 ng/ml) with compound 1, and extracellular-related kinase phosphorylation is reduced by treatment with compound 1 in both basal and EGF-stimulated conditions, suggesting that the observed effect depends on a direct interference with growth factor signaling.
Viola
Santa
S
Department of Experimental and Clinical Pharmacology, University of Catania, Italy.
Merlo
Sara
S
Consoli
Grazia M L
GM
Drago
Filippo
F
Geraci
Corrada
C
Sortino
Maria Angela
MA
D000117:Acetylglucosamine; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D047250:Calixarenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D047250:Calixarenes; D004815:Epidermal Growth Factor; D051417:Focal Adhesion Kinase 1; D000117:Acetylglucosamine