International Journal of Molecular Sciences, 2016, 17(9).

The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

Alina Uifălean, Stefanie Schneider, Philipp Gierok, et al

Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 6, Cluj-Napoca 400349, Romania; et al

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.

《国际分子科学杂志》, 2016

大豆异黄酮使用整体代谢方法对乳腺癌细胞 MCF-7 和 MDA-MB-231的影响

药学院药物分析系，“IuliuHaţieganu”医药和药学大学，路易斯巴斯德街6号，罗马尼亚克卢日 - 纳波卡400349; et al

尽管进行了大量的研究，对大豆异黄酮的化学预防机制的理解仍然具有挑战性。有前景的工具，如代谢组学，可以提供更深入的洞察他们的生化机制。本研究的目的是提供对染料木黄酮，黄豆苷原和大豆种子提取物对雌激素反应性（MCF-7）和雌激素非反应性乳腺癌细胞（MDA-MB-231）诱导的代谢改变的综合评估，使用全球代谢组学方法。 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）测定显示所有测试化合物诱导对MCF-7细胞的双相作用，并且仅对MDA- MB-231细胞。细胞外代谢物的质子核磁共振（1H-NMR）谱和气相色谱 - 质谱（GC-MS）谱的细胞内代谢物证实了所有测试化合物共享相似的代谢机制。将MCF-7细胞暴露于刺激浓度的异黄酮导致6-磷酸葡萄糖酸和核糖5-磷酸的细胞内水平增加，表明可能的戊糖磷酸途径的上调。在暴露于抑制剂量的异黄酮后，观察到葡萄糖摄取的显着降低，特别是对于MCF-7细胞。在MDA-MB-231细胞中，谷氨酰胺摄取被显着限制，导致蛋白质生物合成的改变。了解异黄酮的代谢组学变化代表了在考虑大豆和大豆衍生物作为乳腺癌化学预防中的功能性食品的一个进步。