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Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines
In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331763/ https://www.ncbi.nlm.nih.gov/pubmed/32655277 http://dx.doi.org/10.1177/1178223420913330 |
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author | Amaral de Mascena Costa, Luciana Harmon, Ashlyn C Aguiar Coelho Teixeira, Alvaro Cássio Silva de Lima, Filipe de Sousa Araújo, Silvany Del Piero, Fabio Diógenes da Silva Souza, Helivaldo Filgueiras de Athayde Filho, Petrônio Alves Junior, Severino de Mascena Diniz Maia, Maria Wischral, Aurea Adrião Gomes Filho, Manoel Mathis, J Michael |
author_facet | Amaral de Mascena Costa, Luciana Harmon, Ashlyn C Aguiar Coelho Teixeira, Alvaro Cássio Silva de Lima, Filipe de Sousa Araújo, Silvany Del Piero, Fabio Diógenes da Silva Souza, Helivaldo Filgueiras de Athayde Filho, Petrônio Alves Junior, Severino de Mascena Diniz Maia, Maria Wischral, Aurea Adrião Gomes Filho, Manoel Mathis, J Michael |
author_sort | Amaral de Mascena Costa, Luciana |
collection | PubMed |
description | In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT and crystal violet assays, flow cytometry analysis, electron microscopy characterization, and terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) apoptosis assays. As determined using XTT cell growth and survival assays, MIH 2.4Bl exhibited growth inhibition activity on most breast cancer cell lines tested, compared with normal human mammary epithelial cells. Three breast cancer cell lines (MCF-7, T-47D, and ZR-75-1) showed a more potent sensitivity index to growth inhibition by MIH 2.4Bl than the other breast cancer cell lines. Interestingly, these 3 cell lines were derived from tumors of Luminal A origin and have ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2) positive expression. Additional analysis of cytotoxicity mediated by MIH 2.4Bl was performed using the MCF-7 cell line. MCF-7 cells displayed both time- and dose-dependent decreases in cell growth and survival, with a maximum cytotoxic effect observed at 72 and 96 hours. The MCF-7 cells were also characterized for cell cycle changes upon treatment with MIH 2.4Bl. Using flow cytometry analysis of cell cycle distribution, a treatment-dependent effect was observed; treatment of cells with MIH 2.4Bl increased the G2/M population to 34.2% compared with 0.1% in untreated (control) cells. Ultrastructural analysis of MFC-7 cells treated with MIH 2.4Bl at 2 different concentrations (37.5 and 75 μM) was performed by transmission electron microscopy. Cells treated with 37.5 μM MIH 2.4Bl showed morphologic changes beginning at 6 hours after treatment, while cells treated with 75 μM showed changes beginning at 3 hours after treatment. These changes were characterized by an alteration of nuclear morphology and mitochondrial degeneration consistent with apoptotic cell death. Results of a TUNEL assay performed on cells treated for 96 hours with MIH 2.4Bl supported the observation of apoptosis. Together, these results suggest that MIH 2.4Bl is a promising candidate for treating breast cancer and support further in vitro and in vivo investigation. |
format | Online Article Text |
id | pubmed-7331763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-73317632020-07-10 Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines Amaral de Mascena Costa, Luciana Harmon, Ashlyn C Aguiar Coelho Teixeira, Alvaro Cássio Silva de Lima, Filipe de Sousa Araújo, Silvany Del Piero, Fabio Diógenes da Silva Souza, Helivaldo Filgueiras de Athayde Filho, Petrônio Alves Junior, Severino de Mascena Diniz Maia, Maria Wischral, Aurea Adrião Gomes Filho, Manoel Mathis, J Michael Breast Cancer (Auckl) Original Research In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT and crystal violet assays, flow cytometry analysis, electron microscopy characterization, and terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) apoptosis assays. As determined using XTT cell growth and survival assays, MIH 2.4Bl exhibited growth inhibition activity on most breast cancer cell lines tested, compared with normal human mammary epithelial cells. Three breast cancer cell lines (MCF-7, T-47D, and ZR-75-1) showed a more potent sensitivity index to growth inhibition by MIH 2.4Bl than the other breast cancer cell lines. Interestingly, these 3 cell lines were derived from tumors of Luminal A origin and have ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2) positive expression. Additional analysis of cytotoxicity mediated by MIH 2.4Bl was performed using the MCF-7 cell line. MCF-7 cells displayed both time- and dose-dependent decreases in cell growth and survival, with a maximum cytotoxic effect observed at 72 and 96 hours. The MCF-7 cells were also characterized for cell cycle changes upon treatment with MIH 2.4Bl. Using flow cytometry analysis of cell cycle distribution, a treatment-dependent effect was observed; treatment of cells with MIH 2.4Bl increased the G2/M population to 34.2% compared with 0.1% in untreated (control) cells. Ultrastructural analysis of MFC-7 cells treated with MIH 2.4Bl at 2 different concentrations (37.5 and 75 μM) was performed by transmission electron microscopy. Cells treated with 37.5 μM MIH 2.4Bl showed morphologic changes beginning at 6 hours after treatment, while cells treated with 75 μM showed changes beginning at 3 hours after treatment. These changes were characterized by an alteration of nuclear morphology and mitochondrial degeneration consistent with apoptotic cell death. Results of a TUNEL assay performed on cells treated for 96 hours with MIH 2.4Bl supported the observation of apoptosis. Together, these results suggest that MIH 2.4Bl is a promising candidate for treating breast cancer and support further in vitro and in vivo investigation. SAGE Publications 2020-07-01 /pmc/articles/PMC7331763/ /pubmed/32655277 http://dx.doi.org/10.1177/1178223420913330 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Amaral de Mascena Costa, Luciana Harmon, Ashlyn C Aguiar Coelho Teixeira, Alvaro Cássio Silva de Lima, Filipe de Sousa Araújo, Silvany Del Piero, Fabio Diógenes da Silva Souza, Helivaldo Filgueiras de Athayde Filho, Petrônio Alves Junior, Severino de Mascena Diniz Maia, Maria Wischral, Aurea Adrião Gomes Filho, Manoel Mathis, J Michael Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title | Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title_full | Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title_fullStr | Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title_full_unstemmed | Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title_short | Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines |
title_sort | cytotoxic activity of the mesoionic compound mih 2.4bl in breast cancer cell lines |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331763/ https://www.ncbi.nlm.nih.gov/pubmed/32655277 http://dx.doi.org/10.1177/1178223420913330 |
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