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Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four...

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Autores principales: Guerra, Fabiana Sélos, Dias, Flaviana Rodrigues Fintelman, Cunha, Anna Claudia, Fernandes, Patricia Dias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347180/
https://www.ncbi.nlm.nih.gov/pubmed/34361566
http://dx.doi.org/10.3390/molecules26154414
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author Guerra, Fabiana Sélos
Dias, Flaviana Rodrigues Fintelman
Cunha, Anna Claudia
Fernandes, Patricia Dias
author_facet Guerra, Fabiana Sélos
Dias, Flaviana Rodrigues Fintelman
Cunha, Anna Claudia
Fernandes, Patricia Dias
author_sort Guerra, Fabiana Sélos
collection PubMed
description Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation.
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spelling pubmed-83471802021-08-08 Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer Guerra, Fabiana Sélos Dias, Flaviana Rodrigues Fintelman Cunha, Anna Claudia Fernandes, Patricia Dias Molecules Article Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation. MDPI 2021-07-21 /pmc/articles/PMC8347180/ /pubmed/34361566 http://dx.doi.org/10.3390/molecules26154414 Text en © 2021 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
Guerra, Fabiana Sélos
Dias, Flaviana Rodrigues Fintelman
Cunha, Anna Claudia
Fernandes, Patricia Dias
Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title_full Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title_fullStr Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title_full_unstemmed Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title_short Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer
title_sort benzo[f]indole-4,9-dione derivatives effectively inhibit the growth of triple-negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347180/
https://www.ncbi.nlm.nih.gov/pubmed/34361566
http://dx.doi.org/10.3390/molecules26154414
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