Mictlan-D3: A novel medium sized RGD-Disintegrin obtained from Crotalus mictlantecuhtli venom, in vitro tested against human breast Cancer and endothelial cells.
E Rivas-Mercado, E Neri-Castro, V Zarzosa, L Hernández-Orihuela, F Olvera-Rodríguez, J D Torres-Garza, L Garza-Ocañas
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引用次数: 0
Abstract
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.
期刊介绍：
Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.
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