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BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

BACKGROUND: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell line...

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Autores principales: Bezerra, Patrícia Heloise Alves, Ferreira, Isadora Marques, Franceschi, Beatriz Tinoco, Bianchini, Francine, Ambrósio, Luciana, Cintra, Adélia Cristina O., Sampaio, Suely Vilela, de Castro, Fabíola Attié, Torqueti, Maria Regina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Centro de Estudos de Venenos e Animais Peçonhentos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665320/
https://www.ncbi.nlm.nih.gov/pubmed/31384244
http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0010
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author Bezerra, Patrícia Heloise Alves
Ferreira, Isadora Marques
Franceschi, Beatriz Tinoco
Bianchini, Francine
Ambrósio, Luciana
Cintra, Adélia Cristina O.
Sampaio, Suely Vilela
de Castro, Fabíola Attié
Torqueti, Maria Regina
author_facet Bezerra, Patrícia Heloise Alves
Ferreira, Isadora Marques
Franceschi, Beatriz Tinoco
Bianchini, Francine
Ambrósio, Luciana
Cintra, Adélia Cristina O.
Sampaio, Suely Vilela
de Castro, Fabíola Attié
Torqueti, Maria Regina
author_sort Bezerra, Patrícia Heloise Alves
collection PubMed
description BACKGROUND: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. METHODS: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. RESULTS: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. CONCLUSIONS: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.
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spelling pubmed-66653202019-08-05 BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation Bezerra, Patrícia Heloise Alves Ferreira, Isadora Marques Franceschi, Beatriz Tinoco Bianchini, Francine Ambrósio, Luciana Cintra, Adélia Cristina O. Sampaio, Suely Vilela de Castro, Fabíola Attié Torqueti, Maria Regina J Venom Anim Toxins Incl Trop Dis Research BACKGROUND: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. METHODS: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. RESULTS: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. CONCLUSIONS: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer. Centro de Estudos de Venenos e Animais Peçonhentos 2019-07-29 /pmc/articles/PMC6665320/ /pubmed/31384244 http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0010 Text en This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bezerra, Patrícia Heloise Alves
Ferreira, Isadora Marques
Franceschi, Beatriz Tinoco
Bianchini, Francine
Ambrósio, Luciana
Cintra, Adélia Cristina O.
Sampaio, Suely Vilela
de Castro, Fabíola Attié
Torqueti, Maria Regina
BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title_full BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title_fullStr BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title_full_unstemmed BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title_short BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
title_sort bthtx-i from bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6665320/
https://www.ncbi.nlm.nih.gov/pubmed/31384244
http://dx.doi.org/10.1590/1678-9199-JVATITD-2019-0010
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