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Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is an aggressive form of mammary malignancy currently without satisfactory systemic treatment options. Agents generating reactive oxygen species (ROS), such as ascorbate (Asc) and menadione (Men), especially applied in combination, have been proposed as an altern...

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Autores principales: Bajor, Malgorzata, Graczyk-Jarzynka, Agnieszka, Marhelava, Katsiaryna, Kurkowiak, Malgorzata, Rahman, Arman, Aura, Claudia, Russell, Niamh, Zych, Agata O., Firczuk, Malgorzata, Winiarska, Magdalena, Gallagher, William M., Zagozdzon, Radoslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222372/
https://www.ncbi.nlm.nih.gov/pubmed/32316111
http://dx.doi.org/10.3390/antiox9040320
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author Bajor, Malgorzata
Graczyk-Jarzynka, Agnieszka
Marhelava, Katsiaryna
Kurkowiak, Malgorzata
Rahman, Arman
Aura, Claudia
Russell, Niamh
Zych, Agata O.
Firczuk, Malgorzata
Winiarska, Magdalena
Gallagher, William M.
Zagozdzon, Radoslaw
author_facet Bajor, Malgorzata
Graczyk-Jarzynka, Agnieszka
Marhelava, Katsiaryna
Kurkowiak, Malgorzata
Rahman, Arman
Aura, Claudia
Russell, Niamh
Zych, Agata O.
Firczuk, Malgorzata
Winiarska, Magdalena
Gallagher, William M.
Zagozdzon, Radoslaw
author_sort Bajor, Malgorzata
collection PubMed
description Triple-negative breast cancer (TNBC) is an aggressive form of mammary malignancy currently without satisfactory systemic treatment options. Agents generating reactive oxygen species (ROS), such as ascorbate (Asc) and menadione (Men), especially applied in combination, have been proposed as an alternative anticancer modality. However, their effectiveness can be hampered by the cytoprotective effects of elevated antioxidant enzymes (e.g., peroxiredoxins, PRDX) in cancer. In this study, PRDX1 mRNA and protein expression were assessed in TNBC tissues by analysis of the online RNA-seq datasets and immunohistochemical staining of tissue microarray, respectively. We demonstrated that PRDX1 mRNA expression was markedly elevated in primary TNBC tumors as compared to non-malignant controls, with PRDX1 protein staining intensity correlating with favorable survival parameters. Subsequently, PRDX1 functionality in TNBC cell lines or non-malignant mammary cells was targeted by genetic silencing or chemically by auranofin (AUR). The PRDX1-knockdown or AUR treatment resulted in inhibition of the growth of TNBC cells in vitro. These cytotoxic effects were further synergistically potentiated by the incubation with a combination of the prooxidant agents, Asc and Men. In conclusion, we report that the PRDX1-related antioxidant system is essential for maintaining redox homeostasis in TNBC cells and can be an attractive therapeutic target in combination with ROS-generating agents.
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spelling pubmed-72223722020-05-28 Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells Bajor, Malgorzata Graczyk-Jarzynka, Agnieszka Marhelava, Katsiaryna Kurkowiak, Malgorzata Rahman, Arman Aura, Claudia Russell, Niamh Zych, Agata O. Firczuk, Malgorzata Winiarska, Magdalena Gallagher, William M. Zagozdzon, Radoslaw Antioxidants (Basel) Article Triple-negative breast cancer (TNBC) is an aggressive form of mammary malignancy currently without satisfactory systemic treatment options. Agents generating reactive oxygen species (ROS), such as ascorbate (Asc) and menadione (Men), especially applied in combination, have been proposed as an alternative anticancer modality. However, their effectiveness can be hampered by the cytoprotective effects of elevated antioxidant enzymes (e.g., peroxiredoxins, PRDX) in cancer. In this study, PRDX1 mRNA and protein expression were assessed in TNBC tissues by analysis of the online RNA-seq datasets and immunohistochemical staining of tissue microarray, respectively. We demonstrated that PRDX1 mRNA expression was markedly elevated in primary TNBC tumors as compared to non-malignant controls, with PRDX1 protein staining intensity correlating with favorable survival parameters. Subsequently, PRDX1 functionality in TNBC cell lines or non-malignant mammary cells was targeted by genetic silencing or chemically by auranofin (AUR). The PRDX1-knockdown or AUR treatment resulted in inhibition of the growth of TNBC cells in vitro. These cytotoxic effects were further synergistically potentiated by the incubation with a combination of the prooxidant agents, Asc and Men. In conclusion, we report that the PRDX1-related antioxidant system is essential for maintaining redox homeostasis in TNBC cells and can be an attractive therapeutic target in combination with ROS-generating agents. MDPI 2020-04-16 /pmc/articles/PMC7222372/ /pubmed/32316111 http://dx.doi.org/10.3390/antiox9040320 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bajor, Malgorzata
Graczyk-Jarzynka, Agnieszka
Marhelava, Katsiaryna
Kurkowiak, Malgorzata
Rahman, Arman
Aura, Claudia
Russell, Niamh
Zych, Agata O.
Firczuk, Malgorzata
Winiarska, Magdalena
Gallagher, William M.
Zagozdzon, Radoslaw
Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title_full Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title_fullStr Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title_full_unstemmed Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title_short Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells
title_sort triple combination of ascorbate, menadione and the inhibition of peroxiredoxin-1 produces synergistic cytotoxic effects in triple-negative breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222372/
https://www.ncbi.nlm.nih.gov/pubmed/32316111
http://dx.doi.org/10.3390/antiox9040320
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