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

Author:

Van Petten de Vasconcelos Azevedo Fernanda,Lopes Daiana Silva,Zóia Mariana Alves Pereira,Correia Lucas Ian VelosoORCID,Saito NatieliORCID,Fonseca Belchiolina Beatriz,Polloni Lorena,Teixeira Samuel Cota,Goulart Luiz RicardoORCID,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.

Funder

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

National Council for Scientific and Technological Development

Coordenação de Aperfeicoamento de Pessoal de Nível Superior

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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