title: The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach.
abstract: Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (¹H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention.
authors: Department of Pharmaceutical Analysis, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania. alina.uifalean@umfcluj.ro.|Institute of Biochemistry, Ernst-Moritz-Arndt-University, Felix-Hausdorff Street 4, Greifswald 17487, Germany. alina.uifalean@umfcluj.ro.
authors: Alina
authors: A
authors: Uifălean
authors: Institute of Biochemistry, Ernst-Moritz-Arndt-University, Felix-Hausdorff Street 4, Greifswald 17487, Germany. schneids42@uni-greifswald.de.
authors: Stefanie
authors: S
authors: Schneider
authors: Institute of Biochemistry, Ernst-Moritz-Arndt-University, Felix-Hausdorff Street 4, Greifswald 17487, Germany. gierokp47@uni-greifswald.de.
authors: Philipp
authors: P
authors: Gierok
authors: Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania. corina.ionescu@umfcluj.ro.
authors: Corina
authors: C
authors: Ionescu
authors: Department of Pharmaceutical Analysis, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania. iugac@umfcluj.ro.|MedFuture Research Center for Advanced Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, Louis Pasteur Street 4-6, Gh. Marinescu Street 23, Cluj-Napoca 400349, Romania. iugac@umfcluj.ro.
authors: Cristina Adela
authors: CA
authors: Iuga
authors: Institute of Biochemistry, Ernst-Moritz-Arndt-University, Felix-Hausdorff Street 4, Greifswald 17487, Germany. lalk@uni-greifswald.de.
authors: Michael
authors: M
authors: Lalk
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D061986:MCF-7 Cells; D055442:Metabolome / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D007529:Isoflavones; D010936:Plant Extracts
keywords: 1H-NMR; GC-MS; MTT assay; breast cancer; glucose uptake; glutamine uptake; metabolomics; soy isoflavones