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Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4

BACKGROUND: Anthocyanins (ACNs) are capable of suppressing breast cancer growth; however, investigation on the effect and mechanism of ACNs on epithelial-to-mesenchymal transition (EMT), and cell migration and invasion in breast cancer cells is limited. A complete understanding of those properties m...

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Autores principales: Chen, Dahu, Yuan, Mei, Ye, Qin, Wang, Xing, Xu, Jing, Shi, Guangyi, Hu, Zhaodi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Open Academia 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672442/
https://www.ncbi.nlm.nih.gov/pubmed/33240028
http://dx.doi.org/10.29219/fnr.v64.4240
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author Chen, Dahu
Yuan, Mei
Ye, Qin
Wang, Xing
Xu, Jing
Shi, Guangyi
Hu, Zhaodi
author_facet Chen, Dahu
Yuan, Mei
Ye, Qin
Wang, Xing
Xu, Jing
Shi, Guangyi
Hu, Zhaodi
author_sort Chen, Dahu
collection PubMed
description BACKGROUND: Anthocyanins (ACNs) are capable of suppressing breast cancer growth; however, investigation on the effect and mechanism of ACNs on epithelial-to-mesenchymal transition (EMT), and cell migration and invasion in breast cancer cells is limited. A complete understanding of those properties may provide useful information on of how to use these natural compounds for cancer prevention and treatment. OBJECTIVES: The aim of this work was to investigate the role of cyanidin-3-O-glucoside (Cy3G), one of the most widely distributed ACNs in edible fruits, in the EMT process, and cell migration and invasion of breast cancer cells, and its underlying molecular mechanisms of how Cy3G establishes these functional roles in these cells. METHODS: MDA-MB-231 and MDA-MB-468 breast cancer cells were treated with Cy3G (20 μM) for 24 h, and then the cells were used for cell migration and invasion assay. Western blotting, luciferase assay, ubiquitination assay, gene knockdown, and cycloheximide chase assay were performed to analyze the molecular mechanisms of Cy3G in suppressing EMT, and cell migration and invasion. RESULTS: Cy3G inhibited the EMT process in these cells and significantly suppressed the migration and invasion of breast cancer cells (P ≤ 0.05) by upregulating Krüppel-like factor 4 (KLF4) expression at protein level. KLF4 knockdown in MDA-MB-231 cells did not reveal any change in EMT marker expression, and cell migration and invasion upon treatment with Cy3G (P ≥ 0.05), which strongly indicated that the effects of Cy3G were mediated by KLF4. Furthermore, we determined that Cy3G indirectly upregulated KLF4 expression by downregulating FBXO32, which is the E3 ligase of KLF4. CONCLUSION: Cy3G is a potential anticancer reagent as it can inhibit EMT and breast cancer cell migration and invasion by upregulating KLF4.
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spelling pubmed-76724422020-11-24 Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4 Chen, Dahu Yuan, Mei Ye, Qin Wang, Xing Xu, Jing Shi, Guangyi Hu, Zhaodi Food Nutr Res Original Article BACKGROUND: Anthocyanins (ACNs) are capable of suppressing breast cancer growth; however, investigation on the effect and mechanism of ACNs on epithelial-to-mesenchymal transition (EMT), and cell migration and invasion in breast cancer cells is limited. A complete understanding of those properties may provide useful information on of how to use these natural compounds for cancer prevention and treatment. OBJECTIVES: The aim of this work was to investigate the role of cyanidin-3-O-glucoside (Cy3G), one of the most widely distributed ACNs in edible fruits, in the EMT process, and cell migration and invasion of breast cancer cells, and its underlying molecular mechanisms of how Cy3G establishes these functional roles in these cells. METHODS: MDA-MB-231 and MDA-MB-468 breast cancer cells were treated with Cy3G (20 μM) for 24 h, and then the cells were used for cell migration and invasion assay. Western blotting, luciferase assay, ubiquitination assay, gene knockdown, and cycloheximide chase assay were performed to analyze the molecular mechanisms of Cy3G in suppressing EMT, and cell migration and invasion. RESULTS: Cy3G inhibited the EMT process in these cells and significantly suppressed the migration and invasion of breast cancer cells (P ≤ 0.05) by upregulating Krüppel-like factor 4 (KLF4) expression at protein level. KLF4 knockdown in MDA-MB-231 cells did not reveal any change in EMT marker expression, and cell migration and invasion upon treatment with Cy3G (P ≥ 0.05), which strongly indicated that the effects of Cy3G were mediated by KLF4. Furthermore, we determined that Cy3G indirectly upregulated KLF4 expression by downregulating FBXO32, which is the E3 ligase of KLF4. CONCLUSION: Cy3G is a potential anticancer reagent as it can inhibit EMT and breast cancer cell migration and invasion by upregulating KLF4. Open Academia 2020-09-28 /pmc/articles/PMC7672442/ /pubmed/33240028 http://dx.doi.org/10.29219/fnr.v64.4240 Text en © 2020 Dahu Chen et al. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for any purpose, even commercially, provided the original work is properly cited and states its license.
spellingShingle Original Article
Chen, Dahu
Yuan, Mei
Ye, Qin
Wang, Xing
Xu, Jing
Shi, Guangyi
Hu, Zhaodi
Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title_full Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title_fullStr Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title_full_unstemmed Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title_short Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4
title_sort cyanidin-3-o-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating klf4
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672442/
https://www.ncbi.nlm.nih.gov/pubmed/33240028
http://dx.doi.org/10.29219/fnr.v64.4240
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