Efeito antimetastático em células de câncer de pulmão e antiangiogênico da PLA2 Lys49 MJTX-II, isolada da peçonha de Bothrops moojeni

Abstract

Cancer is characterized by uncontrolled cell division, which escapes the mechanisms of cell cycle control and apoptosis, invades other tissues, promoting angiogenesis and metastasis. Lung cancer is the third most common type of cancer in Brazil and is associated with high incidence and mortality rates, as a result of the aggressiveness sustained by the processes of angiogenesis and metastasis. In this context, several studies have shown that Phospholipases A2 (PLA2) isolated from snake venom have been investigated with the goal of developing future drugs for cancer therapy. In this work we aimed to investigate for the first time the antimetastatic and antiangiogenic effects of MjTX-II, a PLA2 isolated from Bothrops moojeni venom on lung cancer cells and endotelial cells. From cell culture assays in vitro and ex vivo techniques, we demonstrated that PLA2 acts on A549 lung cancer tumor cells, reducing their viability and inhibiting fundamentals processes to their growth and metastasis, such as adhesion, migration, invasion, and decrease of the actin cytoskeleton without significantly interfering with non tumorigenic lung cells (BEAS-2B). Furthermore, it caused alterations in the cell cycle, led to the production of reactive oxygen species, as well as modulated the expression of pro and anti angiogenic genes and decreased the expression of vascular endothelial growth factor (VEGF) in HUVECs endothelial cells. Finally, the toxin also inhibited angiogenesis processesex vivo in an aortic ring model. We therefore conclude that MjTX-II exhibits an antimetastatic and antiangiogenic effect in vitro and ex vivo, representing a biotechnological tool for the study of neoplasms and a promising molecule as a pharmacological model for antitumor therapy.