A New Approach to Inhibiting Triple-Negative Breast Cancer: In Vitro, Ex Vivo and In Vivo Antiangiogenic Effect of BthTx-II, a PLA2-Asp-49 from Bothrops jararacussu Venom

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...

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Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-02, Vol.12 (2), p.258
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:
Angiogenesis
Aorta
Apoptosis
Asp-49 PLA2
Breast cancer
BthTx-II
Cancer therapies
Cell adhesion
Cell culture
Cell division
Cell migration
Cell proliferation
Chorioallantoic membrane
Drug development
Drug dosages
Embryos
Endothelial cells
Germination
Metastasis
Phospholipase A2
Physiology
Signal transduction
Tumor suppression
Tumors
Umbilical vein
Vascular endothelial growth factor
Venom
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Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12020258