Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784677639309492224
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
work_keys_str_mv AT vanpettendevasconcelosazevedofernanda anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT lopesdaianasilva anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT zoiamarianaalvespereira anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT correialucasianveloso anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT saitonatieli anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT fonsecabelchiolinabeatriz anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT pollonilorena anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT teixeirasamuelcota anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT goulartluizricardo anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT demelorodriguesavilaveridiana anewapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT vanpettendevasconcelosazevedofernanda newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT lopesdaianasilva newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT zoiamarianaalvespereira newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT correialucasianveloso newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT saitonatieli newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT fonsecabelchiolinabeatriz newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT pollonilorena newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT teixeirasamuelcota newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT goulartluizricardo newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom
AT demelorodriguesavilaveridiana newapproachtoinhibitingtriplenegativebreastcancerinvitroexvivoandinvivoantiangiogeniceffectofbthtxiiapla2asp49frombothropsjararacussuvenom