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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
Phospholipases A(2) (PLA(2)) 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 repo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961627/ https://www.ncbi.nlm.nih.gov/pubmed/35204758 http://dx.doi.org/10.3390/biom12020258 |
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author | 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 |
author_facet | 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 |
author_sort | Van Petten de Vasconcelos Azevedo, Fernanda |
collection | PubMed |
description | Phospholipases A(2) (PLA(2)) 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. |
format | Online Article Text |
id | pubmed-8961627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89616272022-03-30 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 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 Biomolecules Article Phospholipases A(2) (PLA(2)) 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. MDPI 2022-02-04 /pmc/articles/PMC8961627/ /pubmed/35204758 http://dx.doi.org/10.3390/biom12020258 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961627/ https://www.ncbi.nlm.nih.gov/pubmed/35204758 http://dx.doi.org/10.3390/biom12020258 |
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