A New Approach to Inhibiting Triple-Negative Breast Cancer: In Vitro, Ex Vivo and In Vivo Antiangiogenic Effect of BthTx-II, a PLA 2 -Asp-49 from Bothrops jararacussu Venom

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2022-02, Vol.12 (2)
• Main Authors: Van Petten de Vasconcelos Azevedo, Fernanda, Lopes, Daiana Silva, Zóia, Mariana Alves Pereira, Correia, Lucas Ian Veloso, Saito, Natieli, Fonseca, Belchiolina Beatriz, Polloni, Lorena, Teixeira, Samuel Cota, Goulart, Luiz Ricardo, de Melo Rodrigues Ávila, Veridiana
• Format: Article
• Language: English
• Subjects: Animals; Bothrops - metabolism; Chick Embryo; Crotalid Venoms - pharmacology; Group II Phospholipases A2; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Phospholipases A2 - metabolism; Triple Negative Breast Neoplasms - drug therapy
• ISSN: 2218-273X
• DOI: 10.3390/biom12020258

Phospholipases A (PLA ) represent a superfamily of enzymes widely distributed in living organisms, with a broad spectrum of pharmacological activities and therapeutic potential. Anti-angiogenic strategies have become one of the main tools in fighting cancer. In this sense, the present work reports the inhibition of tumor angiogenesis induced by Asp-49 BthTX-II using in vitro, ex vivo and in vivo approaches. We demonstrate that BthTx-II inhibited cell adhesion, proliferation, and migration of human umbilical vein endothelial cells (HUVEC), as well as caused a reduction in the levels of endothelial growth factor (VEGF) during in vitro angiogenesis assays. BthTx-II was also able to inhibit the sprouting angiogenic process, by the ex vivo germination assay of the aortic ring; in addition, this toxin inhibited the migration and proliferation of HUVEC in co-culture with triple-negative breast cancer cells (e.g., MDA-MB-231 cells). Finally, in vivo tumor suppression and anti-angiogenic activities were analyzed using MDA-MB-231 cells with Matrigel injected into the chorioallantoic membrane of chicken embryo (CAM) for 7 days treatment with BthTx-II, showing a considerable reduction in vessel caliber, on the size and weight of tumors. Together, these results suggest an important antiangiogenic and antitumor role for BthTx-II, as a potential prototype for the development of new tools and antitumor drugs in cancer therapy.