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The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells

Flavonoids have been reported to play an essential role in modulating processes of cellular redox homeostasis such as scavenging ROS. Meanwhile, they also induce oxidative stress that exerts potent antitumor bioactivity. However, the contradiction between these two aspects still remains unclear. In...

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Autores principales: Xi, Xiaomin, Wang, Jiting, Qin, Yue, You, Yilin, Huang, Weidong, Zhan, Jicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032920/
https://www.ncbi.nlm.nih.gov/pubmed/35453307
http://dx.doi.org/10.3390/antiox11040622
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author Xi, Xiaomin
Wang, Jiting
Qin, Yue
You, Yilin
Huang, Weidong
Zhan, Jicheng
author_facet Xi, Xiaomin
Wang, Jiting
Qin, Yue
You, Yilin
Huang, Weidong
Zhan, Jicheng
author_sort Xi, Xiaomin
collection PubMed
description Flavonoids have been reported to play an essential role in modulating processes of cellular redox homeostasis such as scavenging ROS. Meanwhile, they also induce oxidative stress that exerts potent antitumor bioactivity. However, the contradiction between these two aspects still remains unclear. In this study, four typical flavonoids were selected and studied. The results showed that low-dose flavonoids slightly promoted the proliferation of breast cancer cells under normal growth via gradually reducing accumulated oxidative products and demonstrated a synergistic effect with reductants NAC or VC. Besides, low-dose flavonoids significantly reduced the content of ROS and MDA induced by LPS or Rosup but restored the activity of SOD. However, high-dose flavonoids markedly triggered the cell death via oxidative stress as evidenced by upregulated ROS, MDA and downregulated SOD activity that could be partly rescued by NAC pretreatment, which was also confirmed by antioxidative gene expression levels. The underlying mechanism of such induced cell death was pinpointed as apoptosis, cell cycle arrest, accumulated mitochondrial superoxide, impaired mitochondrial function and decreased ATP synthesis. Transcriptomic analysis of apigenin and quercetin uncovered that high-dose flavonoids activated TNF-α signaling, as verified through detecting inflammatory gene levels in breast cancer cells and RAW 264.7 macrophages. Moreover, we identified that BRCA1 overexpression effectively attenuated such oxidative stress, inflammation and inhibited ATP synthesis induced by LPS or high dose of flavonoids possibly through repairing DNA damage, revealing an indispensable biological function of BRCA1 in resisting oxidative damage and inflammatory stimulation caused by exogenous factors.
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spelling pubmed-90329202022-04-23 The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells Xi, Xiaomin Wang, Jiting Qin, Yue You, Yilin Huang, Weidong Zhan, Jicheng Antioxidants (Basel) Article Flavonoids have been reported to play an essential role in modulating processes of cellular redox homeostasis such as scavenging ROS. Meanwhile, they also induce oxidative stress that exerts potent antitumor bioactivity. However, the contradiction between these two aspects still remains unclear. In this study, four typical flavonoids were selected and studied. The results showed that low-dose flavonoids slightly promoted the proliferation of breast cancer cells under normal growth via gradually reducing accumulated oxidative products and demonstrated a synergistic effect with reductants NAC or VC. Besides, low-dose flavonoids significantly reduced the content of ROS and MDA induced by LPS or Rosup but restored the activity of SOD. However, high-dose flavonoids markedly triggered the cell death via oxidative stress as evidenced by upregulated ROS, MDA and downregulated SOD activity that could be partly rescued by NAC pretreatment, which was also confirmed by antioxidative gene expression levels. The underlying mechanism of such induced cell death was pinpointed as apoptosis, cell cycle arrest, accumulated mitochondrial superoxide, impaired mitochondrial function and decreased ATP synthesis. Transcriptomic analysis of apigenin and quercetin uncovered that high-dose flavonoids activated TNF-α signaling, as verified through detecting inflammatory gene levels in breast cancer cells and RAW 264.7 macrophages. Moreover, we identified that BRCA1 overexpression effectively attenuated such oxidative stress, inflammation and inhibited ATP synthesis induced by LPS or high dose of flavonoids possibly through repairing DNA damage, revealing an indispensable biological function of BRCA1 in resisting oxidative damage and inflammatory stimulation caused by exogenous factors. MDPI 2022-03-24 /pmc/articles/PMC9032920/ /pubmed/35453307 http://dx.doi.org/10.3390/antiox11040622 Text en © 2022 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
Xi, Xiaomin
Wang, Jiting
Qin, Yue
You, Yilin
Huang, Weidong
Zhan, Jicheng
The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title_full The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title_fullStr The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title_full_unstemmed The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title_short The Biphasic Effect of Flavonoids on Oxidative Stress and Cell Proliferation in Breast Cancer Cells
title_sort biphasic effect of flavonoids on oxidative stress and cell proliferation in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032920/
https://www.ncbi.nlm.nih.gov/pubmed/35453307
http://dx.doi.org/10.3390/antiox11040622
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