resumo
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.
palavras-chave
ANTIOXIDANT ACTIVITY; OLIVE OIL; GROWTH; PROLIFERATION; ACTIVATION; APOPTOSIS; DEATH
categoria
Biochemistry & Molecular Biology; Chemistry
autores
Garcia-Guasch, M; Escrich, E; Moral, R; Duarte, IF
nossos autores
Iola Melissa Fernandes Duarte
Investigador PrincipalProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed in the scope of the project CICECO-Aveiro Institute of Materials (UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020), financed by national funds through the FCT/MEC (PIDDAC). The NMR spectrometer is part of the National NMR Network (PTNMR), partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC). This research was also funded by "Fundacion Patrimonio Comunal Olivarero (FPCO)" (FPCO2008-165.396; FPCO2013-CF611.084); "Agencia para el Aceite de Oliva del Ministerio de Agricultura, Alimentacion y Medio Ambiente" (AAO2008-165.471); "Organizacion Interprofesional del Aceite de Oliva Espanol (OIAOE)" (OIP2009-CD165.646); and FPCO and OIAOE (FPCO-OIP2016-CF614.087).