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

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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.

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Data Availability

All data needed to support the conclusions are included in this article. Additional data related to this paper can be requested from the corresponding author.

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Acknowledgements

We appreciate all the colleagues who collaborated with us in this study. Especial thanks from Mr. Mohammadkazem Heydari and Mr. Ali Fallah (Mol & Cell Lab., University of Mazandaran, Iran) for the best supports in all parts of our project.

Funding

This study was supported by a grant from the University of Mazandaran, dedicated to the PhD thesis of Esmaeil Samadian (#IranDoc1447431).

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Authors and Affiliations

  1. Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, 47416-95447, Iran

    Esmaeil Samadian & Abasalt Hosseinzadeh Colagar

  2. Metabolic Disorders Research Center, Golestan University of Medical Science, Gorgan, Iran

    Mahdieh Safarzad & Jahanbakhsh Asadi

  3. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Kamran Mansouri

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  1. Esmaeil Samadian
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Contributions

AHC, conception and design, explanation of the data and revising the manuscript; ES, MS, JA and KM performed the experiments, data curation and analysis, and writing-original draft. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Abasalt Hosseinzadeh Colagar.

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This article does not contain any studies with human participants performed by any of the authors.

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This study was approved by the ethics committee of the University of Mazandaran (#IR.UMZ.REC.1397.049) and conducted in accordance with Iran National Committee for Ethics in Biomedical Researches.

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Samadian, E., Colagar, A.H., Safarzad, M. et al. Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis. Mol Biol Rep 50, 4491–4503 (2023). https://doi.org/10.1007/s11033-023-08355-y

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