Efeito antitumoral e antimetastático da PLA2 Lys-49 BthTX-I, de Bothrops jararacussu, em adenocarcinoma pulmonar de células não-pequenas

Abstract

Snake venoms constitute a rich source of proteins and peptides with diverse biological activities, many of which have been explored as biomolecules with potential therapeutic applications. In this study, the protein BthTX-I, a phospholipase A₂-like enzyme isolated from the venom of Bothrops jararacussu, was purified by cation-exchange chromatography using CM-Sepharose Fast Flow. Subsequently, its cytotoxic and antimetastatic effects were evaluated in non-small cell lung adenocarcinoma cells (A549), using non-tumor lung epithelial cells (BEAS-2B) as a control. The cytotoxicity of BthTX-I was initially assessed using MTT, LDH release, and clonogenic assays. In the MTT assay, a significant reduction in cell viability was observed in both cell lines at concentrations above 1.56 μg/mL (Selectivity index (SI) = 0.425). In contrast, the LDH release assay showed that BthTX-I induced greater membrane damage in A549 cells compared to BEAS-2B cells at the lowest concentration tested (0.39 μg/mL). Similarly, the clonogenic assay revealed a significant reduction in the proliferative capacity of A549 cells at 0.39 μg/mL, with no significant effects observed in BEAS-2B cells. Interestingly, BthTX-I caused a slight inhibitory effect on cell adhesion at all tested concentrations in both cell lines. Finally, the antimetastatic potential was investigated through cell migration assays (Wound Healing and Transwell), in which a significant inhibition of A549 cell migration was observed at the lowest tested concentration (0.39 μg/mL), indicating a selective effect on the tumor cell line. Taken together, these results demonstrate that BthTX-I exhibits antitumor potential against lung adenocarcinoma cells by reducing cell viability, proliferation, and migration in a selective manner at low concentrations.