Comparative in vitro and in silico analysis of the ability of basic Asp49 phospholipase A2 and Lys49-phospholipase A2-like myotoxins from Bothrops diporus venom to inhibit the metastatic potential of murine mammary tumor cells and endothelial cell tubulogenesis

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dc.creatorSasovsky, Daniela Jaqueline
dc.creatorAngelina, Emilio
dc.creatorLeiva de Vila, Laura Cristina Ana
dc.creatorBal de Kier Joffé, Elisa Dora
dc.creatorLomonte, Bruno
dc.creatorBustillo, Soledad
dc.date.accessioned2024-09-03T13:05:40Z
dc.date.available2024-09-03T13:05:40Z
dc.date.issued2024
dc.description.abstractSnake venoms are a complex mixture of proteins and polypeptides that represent a valuable source of potential molecular tools for understanding physiological processes for the development of new drugs. In this study two major PLA2s, named PLA2-I (Asp49) and PLA2-II (Lys49), isolated from the venom of Bothrops diporus from Northeastern Argentina, have shown cytotoxic effects on LM3 murine mammary tumor cells, with PLA2-II-like exhibiting a stronger effect compared to PLA2-I. At sub-cytotoxic levels, both PLA2s inhibited adhesion, migration, and invasion of these adenocarcinoma cells. Moreover, these toxins hindered tubulogenesis in endothelial cells, implicating a potential role in inhibiting tumor angiogenesis. All these inhibitory effects were more pronounced for the catalytically-inactive toxin. Additionally, in silico studies strongly suggest that this PLA2-II-like myotoxin could effectively block fibronectin binding to the integrin receptor, offering a dual advantage over PLA2-I in interacting with the αVβ3 integrin. In conclusion, this study reports for the first time, integrating both in vitro and in silico approaches, a comparative analysis of the antimetastatic and antiangiogenic potential effects of two isoforms, an Asp49 PLA2-I and a Lys49 PLA2-II-like, both isolated from Bothrops diporus venom.
dc.description.procedenceVicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)
dc.description.procedenceVicerrectoría de Docencia::Salud::Facultad de Microbiología
dc.identifier.citationhttps://www.sciencedirect.com/science/article/abs/pii/S0009279724003636?via%3Dihub
dc.identifier.doi10.1016/j.cbi.2024.111217
dc.identifier.issn0009-2797
dc.identifier.issn1872-7786
dc.identifier.urihttps://hdl.handle.net/10669/99809
dc.language.isoeng
dc.rightsacceso restringido
dc.sourceChemico-Biological Interactions, 402(1), 1-10
dc.subjectCELL
dc.subjectADHESION
dc.subjectMIGRATION
dc.subjectINVASION
dc.titleComparative in vitro and in silico analysis of the ability of basic Asp49 phospholipase A2 and Lys49-phospholipase A2-like myotoxins from Bothrops diporus venom to inhibit the metastatic potential of murine mammary tumor cells and endothelial cell tubulogenesis
dc.typeartículo original

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