Isolation of an Anti–tumour Disintegrin: Dabmaurin–1, a Peptide Lebein–1–like, from Daboia mauritanica Venom

Abstract

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 Daboia mauritanica, 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 MatrigelTM. 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 Macrovipera lebetina 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.

The Effects of αvβ3 Integrin Blockage in Breast Tumor and Endothelial Cells under Hypoxia In Vitro

“…Previous studies have shown the inhibitory effects on cell migration of other snake venom-derived proteins, including RGD disintegrins such as r-majostin from Crotalus scutulaus scutulatus and r-virisdistatin from Crotalus viridis viridis [56], tzabcanin from C.simus [57], dabmaurin-1 from Daboia mauritanica [58], and disintegrins from Crotalus totonacus [59] and Bothrops alternatus [60] for different types of tumor cells. These studies, however, were performed in normoxia only.…”

Therapeutics Approaches of Invertebrate Animal Toxins: A Review

“…This inhibitor stops formation of new blood vessels or anti-angiogenesis effects [66]. It prevents HT-29 colorectal cancer cell migration [67]. Sea Anemone secretions are actinoporins Sticholysins I and II (Sts, StI/II), which interact with biological membranes of cells and form pores.…”

Snake Venom Metalloproteinases (SVMPs): A structure-function update

“…Recently, Montealegre-Sanchez and co-workers reported that Lansbermin-l, a low molecular weight RGD-disintegrin from Porthidium lansbergii lansbergii , inhibited the adhesion and migration of MCF7 and MDA-DB 231 breast cancer cells by interfering with α 2 or β 1 -containing integrins ( Montealegre-Sánchez et al, 2019 ). Furthermore, Chalier et al (2020) characterized the RGD-disintegrin Dabmaurin-1 isolated from Daboia mauritanica snake. Dabmaurin-1 inhibited HMEC proliferation, adhesion and migration to several ECM components, as well as tube formation after interaction with β 1 -containing integrins ( Chalier et al, 2020 ).…”

“…Furthermore, Chalier et al (2020) characterized the RGD-disintegrin Dabmaurin-1 isolated from Daboia mauritanica snake. Dabmaurin-1 inhibited HMEC proliferation, adhesion and migration to several ECM components, as well as tube formation after interaction with β 1 -containing integrins ( Chalier et al, 2020 ). Additionally, in our laboratory, we demonstrated that Dis Ba -01, a RGD-disintegrin, inhibited cell migration and adhesion in murine breast tumor cell line 4T1BM2.…”