Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin

The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the meta...

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Main Authors: Maite Garcia-Guasch, Eduard Escrich, Raquel Moral, Iola F. Duarte
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/28/9/3886
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author Maite Garcia-Guasch
Eduard Escrich
Raquel Moral
Iola F. Duarte
author_facet Maite Garcia-Guasch
Eduard Escrich
Raquel Moral
Iola F. Duarte
author_sort Maite Garcia-Guasch
collection DOAJ
description The aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.
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spelling doaj.art-93852dd008e34086a6885ba9ecfd6a922023-11-17T23:24:47ZengMDPI AGMolecules1420-30492023-05-01289388610.3390/molecules28093886Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and LuteolinMaite Garcia-Guasch0Eduard Escrich1Raquel Moral2Iola F. Duarte3Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, SpainPhysiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, SpainPhysiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, 08193 Barcelona, SpainCICECO—Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, PortugalThe aim of this study was to investigate the effects of two phenolic compounds found in extra virgin olive oil, hydroxytyrosol (HT) and luteolin (LUT), on the metabolism of breast cancer (BC) cells of different molecular subtypes. An untargeted metabolomics approach was used to characterize the metabolic responses of both triple-negative MDA-MB-231 cells and hormone-responsive MCF-7 cells to treatment with these phenols. Notably, while some effects were common across both cell types, others were dependent on the cell type, highlighting the importance of cellular metabolic phenotype. Common effects included stimulation of mitochondrial metabolism, acetate production, and formate overflow. On the other hand, glucose metabolism and lactate production were differentially modulated. HT and LUT appeared to inhibit glycolysis and promote the hexosamine biosynthetic pathway in MDA-MB-231 cells, while MCF-7 cells exhibited higher glycolytic flux when treated with phenolic compounds. Another significant difference was observed in lipid metabolism. Treated MDA-MB-231 cells displayed increased levels of neutral lipids (likely stored in cytosolic droplets), whereas treatment of MCF-7 cells with HT led to a decrease in triacylglycerols. Additionally, glutathione levels increased in MDA-MB-231 cells treated with HT or LUT, as well as in MCF-7 cells treated with LUT. In contrast, in HT-treated MCF-7 cells, glutathione levels decreased, indicating different modulation of cellular redox status. Overall, this work provides new insights into the metabolic impact of HT and LUT on different BC cell subtypes, paving the way for a better understanding of the nutritional relevance of these phenolic compounds in the context of BC prevention and management.https://www.mdpi.com/1420-3049/28/9/3886breast cancermetabolismhydroxytyrosolluteolinEVOO phenolic compounds
spellingShingle Maite Garcia-Guasch
Eduard Escrich
Raquel Moral
Iola F. Duarte
Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
Molecules
breast cancer
metabolism
hydroxytyrosol
luteolin
EVOO phenolic compounds
title Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
title_full Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
title_fullStr Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
title_full_unstemmed Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
title_short Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
title_sort metabolomics insights into the differential response of breast cancer cells to the phenolic compounds hydroxytyrosol and luteolin
topic breast cancer
metabolism
hydroxytyrosol
luteolin
EVOO phenolic compounds
url https://www.mdpi.com/1420-3049/28/9/3886
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