Disintegrins extracted from totonacan rattlesnake (Crotalus totonacus) venom and their anti-adhesive and anti-migration effects on MDA-MB-231 and HMEC-1 cells

Disintegrins extracted from totonacan rattlesnake (Crotalus totonacus) venom and their anti-adhesive and anti-migration effects on MDA-MB-231 and HMEC-1 cells

Disintegrins are low molecular weight cysteine-rich proteins (4–14 kDa) that are isolated mainly from viperid snake venom. Due to their potential as lead compounds for binding and blocking integrin receptors, snake venom disintegrins have become one of the most studied venom protein families. The ai...

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Bibliographic Details
Published in:Toxicology in vitro Vol. 65; p. 104809
Main Authors: Rivas Mercado, E., Neri Castro, E., Bénard Valle, M., Rucavado-Romero, A., Olvera Rodríguez, A., Zamudio Zuñiga, F., Alagón Cano, A., Garza Ocañas, L.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-06-2020
Elsevier Science Ltd
Subjects:
Adhesion
Angiogenesis
Animals
Blocking
Cell adhesion
Cell adhesion & migration
Cell Adhesion - drug effects
Cell Line
Cell lines
Cell migration
Cell Movement - drug effects
Cell Survival - drug effects
Crotalid Venoms - chemistry
Crotalus
Crotalus totonacus
Disintegrins - isolation & purification
Disintegrins - pharmacology
Extracellular matrix
Fibronectin
Humans
Integrins
Isoforms
Laminin
Lead compounds
Low molecular weights
MDA-MB-231 and HMEC-1 cells
Molecular weight
Protein families
Proteins
Receptors
Reptilian Proteins - isolation & purification
Reptilian Proteins - pharmacology
Snake venom disintegrin
Snakes
Totonacin
Venom
Vitronectin
Wound Healing - drug effects
Totonacin
Snake venom disintegrin
MDA-MB-231 and HMEC-1 cells
Crotalus totonacus
Cell migration
Cell adhesion
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Summary:Disintegrins are low molecular weight cysteine-rich proteins (4–14 kDa) that are isolated mainly from viperid snake venom. Due to their potential as lead compounds for binding and blocking integrin receptors, snake venom disintegrins have become one of the most studied venom protein families. The aim of this study was to obtain disintegrins from C. totonacus venom and evaluate their capability to bind and block integrin receptors. The C. totonacus disintegrin fraction (totonacin) represents two disintegrin isoforms obtained from C. totonacus venom. These disintegrins showed extracellular-matrix (ECM) protein adhesion and migration inhibitory effects on MDA-MB-231 and HMEC-1 cells. Totonacin (3 μM) inhibited MDA-MB-231 cell adhesion to the ECM proteins, fibronectin, vitronectin, and laminin by 31.2, 44.0, and 32.1, respectively. Adhesion inhibition to fibronectin, vitronectin, and laminin observed on HMEC-1 cells was 42.8, 60.8, and 51%, respectively. In addition, totonacin (3 μM) significantly inhibited MDA-MB-231 and HMEC-1 cell migration (41.4 and 48.3%, respectively). Totonacin showed more potent cell adhesion inhibitory activity toward vitronectin in both cell lines. These results suggest a major affinity of totonacin toward αVβ3, α8β1, αVβ5, αVβ1, and αIIbβ3 integrins. In addition, the inhibitory effect observed on MDA-MB-231 and HMEC-1 cell migration reinforces the evidence of an interaction between these disintegrins and αVβ3 integrin, which plays a key role in migration and angiogenesis. •Totonacin inhibits cell adhesion to fibronectin, vitronectin, and laminin.•Totonacin has low cytotoxicity levels at concentrations of 0.09–3 μM.•Totonacin could antagonize one or more of the five integrin VN receptors.•Totonacin is a potential anti-metastatic agent.•Totonacin significantly inhibited cell migration in the cell lines tested.
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content type line 23
ISSN:0887-2333
1879-3177
DOI:10.1016/j.tiv.2020.104809