Metabolomics Insights into the Differential Response of Breast Cancer Cells to the Phenolic Compounds Hydroxytyrosol and Luteolin
Garcia-Guasch, Maite (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Escrich, Eduard (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Moral Cabrera, Raquel (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Duarte, Iola F. (University of Aveiro. Department of Chemistry)

Date:	2023
Abstract:	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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breast cancer ; Metabolism ; Hydroxytyrosol ; Luteolin ; EVOO phenolic compounds
Published in:	Molecules, Vol. 28, Issue 9 (May 2023) , art. 3886, ISSN 1420-3049

DOI: 10.3390/molecules28093886
PMID: 37175295

17 p, 2.8 MB

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