Inhibitory Potency of UDA Lectin on Neovascularization: A Biomolecule for Carbohydrate-Mediated Targeting of Angiogenesis

Abstract

Abstract Background Cellular vascularization processes including proliferation, migration, and tube formation are selectively the purpose of current angiogenic inhibitors. In this study, we investigated the impact of Urtica dioica agglutinin (UDA) on the cellular vascularization processes events. Methods and Results Different concentrations of UDA were treated on various normal (HUVEC, MCF-10A and HDF from human and L-929 from mouse) and cancer (A431 and U87 from human and 4T1 from mouse) cell lines at different times. The MTT, cell migration assay, differentiation of endothelial cells, and expression of VEGF-A/VEGF-R2 and integrin α2 were evaluated. The MTT results demonstrated that UDA was non-toxic on normal cells whereas this lectin was able to prevent the growth of neoplastic cells. The migratory capacity of HUVECs and U87 Glioblastoma cells was inhibited by UDA in wound repair model. This lectin was a preventive agent for HUVECs-induced vessel sprouting in Collagen-cytodex matrix. Also, down-regulation of the VEGF-integrin cross-talk in HUVECs under the UDA treatment confirmed the anti-angiogenic activity of this molecule. Conclusions Based on our findings, UDA may have an effect on the proliferation of cancer cells and vascularization events with minimal toxicity on normal cells through binding glyco-conjugates which bear GlcNAc/Man oligomer like EGFR. This is a blue clue for the angiogenesis-related therapeutic importance of UDA.