Mictlan-D3: A novel medium sized RGD-Disintegrin obtained from Crotalus mictlantecuhtli venom, in vitro tested against human breast Cancer and endothelial cells

• Published in: Toxicology in vitro 2025-04, Vol.104, p.105987, Article 105987
• Main Authors: Rivas-Mercado, E., Neri-Castro, E., Zarzosa, V., Hernández-Orihuela, L., Olvera-Rodríguez, F., Torres-Garza, J.D., Garza-Ocañas, L.
• Format: Article
• Language: English
• Subjects: Cell adhesion; Cell migration; Crotalus mictlantecuhtli; MDA-MB-231 and HMEC-1 cells; Mictlan-D3; RGD-medium size disintegrin
• ISSN: 0887-2333; 1879-3177; 1879-3177
• DOI: 10.1016/j.tiv.2024.105987

Disintegrins are small non-enzymatic proteins present often at low concentration in the venom of viperid snakes. Isolated disintegrins are known for their lack of toxicity as well as their capacity to antagonize integrin receptors. Integrins are a major family of heterodimeric cell surface receptors that mediate cell-cell and cell-extracellular matrix (ECM) interactions. Integrins regulate key functions in cancer pathology and also tumor development. The aim of this study consisted in the isolation and characterization of disintegrins from rattlesnake new species Crotalus mictlantecuhtli venom. A disintegrin fraction obtained by RP-HPLC and named mictlan-D3, consist in two isoforms of 7439 and 7509 Da with 72 amino acid sequence containing the RGD binding motif. Mictlan-D3 inhibited MDA-MB-231 and HMEC-1 cell adhesion to laminin (LN), fibronectin (FN) and vitronectin (VN), highest inhibition was on MDA-MB-231 cell adhesion to LN by 81 % at 1 μM. The blockade of ⍺Vβ3 integrin was evaluated by wound healing migration assay. Mictlan-D3 inhibited MDA-MB-231 cell migration by 80 % and 38 % after 24 and 72 h of incubation respectively. HMEC-1 cell migration was inhibited by 67.6 % and 27.9 % after 24 and 72 h of incubation. Additionally, mictlan-D3. This work represent the first characterization of disintegrins from the Crotalus mictlantecuhtli venom. •Mictlan-D3 a novel medium sized RGD-disintegrin obtained from Crotalus mictlantecuhtli venom.•Mictlan-D3 inhibits migration and adhesion of MDA-MB-231 and HMEC-1 to laminin.•Mictlan-D3 exhibited sustained activity for over 72 h.•Potential therapeutic targets for anti-migratory and anti-invasive cancer treatments.•Expansion of the viperid protein inventory.