Antiangiogenic effects of phospholipase A2 Lys49 BnSP-7 from Bothrops pauloensis snake venom on endothelial cells: An in vitro and ex vivo approach

Toxicol In Vitro. 2021 Apr:72:105099. doi: 10.1016/j.tiv.2021.105099. Epub 2021 Jan 22.

Abstract

Antiangiogenic strategies are promising tools for cancer treatment and several other disorders. In this sense, phospholipases A2 (PLA2s) from snake venom have been described to possess antiangiogenic properties. In this study, we evaluated both in vitro and ex vivo antiangiogenic effects induced by BnSP-7, a Lys49 PLA2 isolated from Bothrops pauloensis snake venom. BnSP-7 was able to inhibit endothelial cell (HUVEC) proliferation, which was indeed confirmed by a modulation of cell cycle progression. Interestingly, BnSP-7 also inhibited the adhesion and migration of HUVECs and blocked in vitro angiogenesis in a VEGF-dependent manner, an important proangiogenic factor. Finally, BnSP-7 was capable of inhibiting sprouting angiogenic process through an ex vivo aortic ring assay. Taken together, these results indicate that BnSP-7 has potent in vitro and ex vivo antiangiogenic effect.

Keywords: Antiangiogenic; BnSP-7; Bothrops pauloensis; Cancer; PLA(2).

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Aorta / drug effects
  • Bothrops
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Crotalid Venoms
  • Group II Phospholipases A2 / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Mice
  • Reptilian Proteins / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Crotalid Venoms
  • Reptilian Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Group II Phospholipases A2
  • Lys49-phospholipase A2, Bothrops neuwiedi pauloensis