PLA 2 -MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells

• Published in: Toxicon (Oxford) 2024-05, Vol.243, p.107742
• Main Authors: Santos, Luísa Carregosa, Oliveira, Vinícius Queiroz, Teixeira, Samuel Cota, Correia, Thiago Macedo Lopes, Andrade, Leonardo Oliveira Silva Bastos, Polloni, Lorena, Marques, Lucas Miranda, Clissa, Patrícia Bianca, Baldo, Cristiani, Ferro, Eloisa Amália Vieira, Gusmão, Amélia Cristina Mendes de Magalhães, Silva, Marcelo José Barbosa, Sanabani, Sabri Saeed, Ávila, Veridiana de Melo Rodrigues, Lopes, Daiana Silva
• Format: Article
• Language: English
• Subjects: A549 Cells; Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Agents - pharmacology; Bothrops; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Crotalid Venoms; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Lung Neoplasms - drug therapy; Neovascularization, Pathologic - drug therapy; Phospholipases A2 - pharmacology; Reactive Oxygen Species - metabolism; Vascular Endothelial Growth Factor A - metabolism; Venomous Snakes
• ISSN: 1879-3150
• DOI: 10.1016/j.toxicon.2024.107742

Phospholipases A (PLA s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA isolated from Bothrops moojeni venom, on lung cancer and endothelial cells. Using in vitro and ex vivo approaches, we demonstrated that MjTX-II reduced cell proliferation and inhibited fundamental processes for lung cancer cells (A549) growth and metastasis, such as adhesion, migration, invasion, and actin cytoskeleton decrease, without significantly interfering with non-tumorigenic lung cells (BEAS-2B). Furthermore, MjTX-II caused cell cycle alterations, increased reactive oxygen species production, modulated the expression of pro- and antiangiogenic genes, and decreased vascular endothelial growth factor (VEGF) expression in HUVECs. Finally, MjTX-II inhibited ex vivo angiogenesis processes in an aortic ring model. Therefore, we conclude that MjTX-II exhibits antimetastatic and antiangiogenic effects in vitro and ex vivo and represents a molecule that hold promise as a pharmacological model for antitumor therapy.