Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells

Abstract This work shows the antitumor and antimetastatic effects of BthTX-II, an Asp-49 PLA 2 from Bothrops jararacussu venom, on MDA-MB-231 human triple negative breast cancer cells. BthTX-II caused a dose-dependent cell death of MDA-MB-231 cells when compared with the non-tumorigenic breast cells by inducing apoptosis and autophagy. BthTX-II was also able to decrease the proliferation and to inhibit cell cycle progression. We also observed an upregulation of the ATM gene, which is responsible for cell-cycle arrest and DNA repair such as CCND1 , CCNE1 , CDC25A , E2F1 , AKT1 and AKT3 . Interestingly, BthTX-II inhibited invasion, migration and 3D cell growth of MDA-MB-231 cells, as well as inhibited the epithelial–mesenchymal transition (EMT) of this cell by increasing E-cadherin ( CDH - 1 ) and decreasing TWIST1 , CTNNB1 , vimentin and cytokeratin-5 expression. In conclusion, these results showed that BthTX-II displays antitumor and antimetastatic effects on MDA-MB-231 cells and may be useful for the development of new approaches and therapeutic strategies to manage triple negative breast cancer.