Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis

Abstract

Background: Current angiogenesis inhibitors target cellular vascularization processes, including proliferation, migration, and tube formation. In this study, we investigated the impact of Urtica dioica agglutinin (UDA) on the cellular vascularization process.

Methods and results: Various concentrations of UDA were applied to normal (HUVEC, MCF-10 A, and HDF from humans, and L-929 from mice) and cancer (A431 and U87 from humans, and 4T1 from mice) cell lines at different times. The MTT, cell migration assay, differentiation of endothelial cells, expression of VEGF-A/VEGF-R2, and integrin α2 were evaluated. The MTT results demonstrated that UDA was non-toxic to normal cells while inhibiting the growth of neoplastic cells. The migratory capacity of HUVECs and U87 glioblastoma cells was inhibited by UDA in the wound repair model. This lectin inhibited HUVEC-induced vessel sprouting in the collagen-cytodex matrix. In addition, UDA treatment reduced VEGF-integrin cross-talk in HUVECs, confirming the anti-angiogenic activity of this molecule.

Conclusions: Based on our findings, UDA may have an effect on cancer cell proliferation and vascularization events while causing minimal toxicity to normal cells via binding glyco-conjugates containing GlcNAc/man oligomers like EGFR. This is a blue clue for the angiogenesis-related therapeutic importance of UDA.

Keywords: Angiogenesis; Cell migration; Cyto-toxicity; UDA; VEGF-integrin axis.