PLA2-MjTX-II from Bothrops moojeni snake venom exhibits antimetastatic and antiangiogenic effects on human lung cancer cells

Toxicon. 2024 May 28:243:107742. doi: 10.1016/j.toxicon.2024.107742. Epub 2024 May 4.

Abstract

Phospholipases A2 (PLA2s) from snake venom possess antitumor and antiangiogenic properties. In this study, we evaluated the antimetastatic and antiangiogenic effects of MjTX-II, a Lys49 PLA2 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.

Keywords: Angiogenic; Lung cancer; MjTX-II; Phospholipases A(2); Snake venom.

MeSH terms

  • 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

Supplementary concepts

  • Bothrops moojeni