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Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important inte...

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Autores principales: Wagner, Mônica Silveira, Schultze, Eduarda, Oliveira, Thais Larre, de Leon, Priscila Marques Moura, Thurow, Helena Strelow, Campos, Vinicius Farias, Oliveira, Isabel, de Souza, Diego, Rodrigues, Oscar Endrigo Dorneles, Collares, Tiago, Seixas, Fabiana Kömmling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262369/
https://www.ncbi.nlm.nih.gov/pubmed/30524958
http://dx.doi.org/10.3389/fonc.2018.00525
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author Wagner, Mônica Silveira
Schultze, Eduarda
Oliveira, Thais Larre
de Leon, Priscila Marques Moura
Thurow, Helena Strelow
Campos, Vinicius Farias
Oliveira, Isabel
de Souza, Diego
Rodrigues, Oscar Endrigo Dorneles
Collares, Tiago
Seixas, Fabiana Kömmling
author_facet Wagner, Mônica Silveira
Schultze, Eduarda
Oliveira, Thais Larre
de Leon, Priscila Marques Moura
Thurow, Helena Strelow
Campos, Vinicius Farias
Oliveira, Isabel
de Souza, Diego
Rodrigues, Oscar Endrigo Dorneles
Collares, Tiago
Seixas, Fabiana Kömmling
author_sort Wagner, Mônica Silveira
collection PubMed
description Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important intermediates applied in organic synthesis. Our objective was to investigate the effect and the underlying cell death mechanisms of AZT and its derivatives, in human breast cancer cell lines. The inhibitory effect of AZT and derivatives (1072, 1073, and 1079) was determined by MTT assay (0.1, 1, 10, 50, and 100 μM for concentrations and times 4, 24, 48, and 72 h) and Live/Dead in tumor cell lines MCF-7, MDA-MB 231 and also in non-tumor cell line CHO. Gene expression profiles related to apoptosis were investigated by qRT-PCR and induction of apoptosis was investigated by flow cytometry. MTT and Live/Dead assays showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 50 and 100 μM in tumor cell lines MCF-7 and MDA-MB 231 while the commercial AZT presented a low antitumoral potential in all strains tested. In flow cytometry analysis we demonstrated that derivatives of AZT induced apoptosis, with an increase in both initial and late stages in both tumor cell lines evaluated, especially in MDA-MB 231. Our data show that the AZT derivative 1072 increased the expression of transcripts of the genes caspase 3 and 8 in MDA-MB 231 cell line when compared to control, suggesting that the extrinsic pathway of apoptosis was activated. In conclusion, derivatives of AZT, especially 1072, induce cytotoxicity in vitro in the triple negative breast cancer cell line through activation of the extrinsic pathway of apoptosis. These compounds containing selenium in its formulation are potential therapeutic agents for breast cancer.
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spelling pubmed-62623692018-12-06 Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line Wagner, Mônica Silveira Schultze, Eduarda Oliveira, Thais Larre de Leon, Priscila Marques Moura Thurow, Helena Strelow Campos, Vinicius Farias Oliveira, Isabel de Souza, Diego Rodrigues, Oscar Endrigo Dorneles Collares, Tiago Seixas, Fabiana Kömmling Front Oncol Oncology Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important intermediates applied in organic synthesis. Our objective was to investigate the effect and the underlying cell death mechanisms of AZT and its derivatives, in human breast cancer cell lines. The inhibitory effect of AZT and derivatives (1072, 1073, and 1079) was determined by MTT assay (0.1, 1, 10, 50, and 100 μM for concentrations and times 4, 24, 48, and 72 h) and Live/Dead in tumor cell lines MCF-7, MDA-MB 231 and also in non-tumor cell line CHO. Gene expression profiles related to apoptosis were investigated by qRT-PCR and induction of apoptosis was investigated by flow cytometry. MTT and Live/Dead assays showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 50 and 100 μM in tumor cell lines MCF-7 and MDA-MB 231 while the commercial AZT presented a low antitumoral potential in all strains tested. In flow cytometry analysis we demonstrated that derivatives of AZT induced apoptosis, with an increase in both initial and late stages in both tumor cell lines evaluated, especially in MDA-MB 231. Our data show that the AZT derivative 1072 increased the expression of transcripts of the genes caspase 3 and 8 in MDA-MB 231 cell line when compared to control, suggesting that the extrinsic pathway of apoptosis was activated. In conclusion, derivatives of AZT, especially 1072, induce cytotoxicity in vitro in the triple negative breast cancer cell line through activation of the extrinsic pathway of apoptosis. These compounds containing selenium in its formulation are potential therapeutic agents for breast cancer. Frontiers Media S.A. 2018-11-14 /pmc/articles/PMC6262369/ /pubmed/30524958 http://dx.doi.org/10.3389/fonc.2018.00525 Text en Copyright © 2018 Wagner, Schultze, Oliveira, de Leon, Thurow, Campos, Oliveira, Souza, Rodrigues, Collares and Seixas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wagner, Mônica Silveira
Schultze, Eduarda
Oliveira, Thais Larre
de Leon, Priscila Marques Moura
Thurow, Helena Strelow
Campos, Vinicius Farias
Oliveira, Isabel
de Souza, Diego
Rodrigues, Oscar Endrigo Dorneles
Collares, Tiago
Seixas, Fabiana Kömmling
Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title_full Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title_fullStr Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title_full_unstemmed Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title_short Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line
title_sort revitalizing the azt through of the selenium: an approach in human triple negative breast cancer cell line
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262369/
https://www.ncbi.nlm.nih.gov/pubmed/30524958
http://dx.doi.org/10.3389/fonc.2018.00525
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