Isolation of an Anti–tumour Disintegrin: Dabmaurin–1, a Peptide Lebein–1–like, from <i>Daboia mauritanica</i> Venom
oleh: Florence Chalier, Laura Mugnier, Marion Tarbe, Soioulata Aboudou, Claude Villard, Hervé Kovacic, Didier Gigmes, Pascal Mansuelle, Harold de Pomyers, José Luis, Kamel Mabrouk
| Format: | Article |
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| Diterbitkan: | MDPI AG 2020-02-01 |
Deskripsi
In the soft treatment of cancer tumours, consequent downregulation of the malignant tissue angiogenesis constitutes an efficient way to stifle tumour development and metastasis spreading. As angiogenesis requires integrin−promoting endothelial cell adhesion, migration, and vessel tube formation, integrins represent potential targets of new therapeutic anti−angiogenic agents. Our work is a contribution to the research of such therapeutic disintegrins in animal venoms. We report isolation of one peptide, named Dabmaurin−1, from the hemotoxic venom of snake <i>Daboia mauritanica</i>, and we evaluate its potential anti−tumour activity through in vitro inhibition of the human vascular endothelial cell HMECs functions involved in tumour angiogenesis. Dabmaurin−1 altered, in a dose−dependent manner, without any significant cytotoxicity, HMEC proliferation, adhesion, and their mesenchymal migration onto various extracellular matrix proteins, as well as formation of capillary−tube mimics on Matrigel<sup>TM</sup>. Via experiments involving HMEC or specific cancers cells integrins, we demonstrated that the above Dabmaurin−1 effects are possibly due to some anti−integrin properties. Dabmaurin−1 was demonstrated to recognize a broad panel of prooncogenic integrins (αvβ6, αvβ3 or αvβ5) and/or particularly involved in control of angiogenesis (α5β1, α6β4, αvβ3 or αvβ5). Furthermore, mass spectrometry and partial N−terminal sequencing of this peptide revealed, it is close to Lebein−1, a known anti−β1 disintegrin from <i>Macrovipera lebetina</i> venom. Therefore, our results show that if Dabmaurin−1 exhibits in vitro apparent anti−angiogenic effects at concentrations lower than 30 nM, it is likely because it acts as an anti−tumour disintegrin.