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- Title
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.
- 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
- Abstract
Phospholipases A2 (PLA2) 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.
- Subjects
TRIPLE-negative breast cancer; CHICKEN embryos; ENDOTHELIAL growth factors; BOTHROPS; VENOM; CHORIOALLANTOIS
- Publication
Biomolecules (2218-273X), 2022, Vol 12, Issue 2, p258
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom12020258