Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
OMICS. 2011 Jan-Feb;15(1-2):9-14. doi: 10.1089/omi.2010.0114. Epub 2011 Jan 17.
Resveratrol is a naturally occurring anticancer compound present in grapes and wine with antiproliferative properties against breast cancer cells and xenografts. Our objective was to investigate the metabolic alterations that characterize the effects of resveratrol in the human breast cancer cell lines MCF-7 and MDA-MB-231 using high-throughput liquid chromatography-based mass spectrometry. In both cell lines, growth inhibition was dose dependent and accompanied by substantial metabolic changes. For all 21 amino acids analyzed levels increased more than 100-fold at a resveratrol dose of 100 μM with far lower concentrations in MDA-MB-231 compared to MCF-7 cells. Among the biogenic amines and modified amino acids (n = 16) resveratrol increased the synthesis of serotonin, kynurenine, and spermindine in both cell lines up to 61-fold indicating that resveratrol strongly interacts with cellular biogenic amine metabolism. Among the eicosanoids and oxidized polyunsaturated fatty acids (n = 17) a pronounced increase in arachidonic acid and its metabolite 12S-HETE was observed in MDA-MB-231 and to a lesser extent in MCF-7 cells, indicating release from cell membrane phospholipids upon activation of phospholipase A₂ and subsequent metabolism by 12-lipoxygenase. In conclusion, metabolomic analysis elucidated several small molecules as markers for the response of breast cancer cells to resveratrol.
白藜芦醇是一种天然存在的抗癌化合物，存在于葡萄和葡萄酒中，具有抗乳腺癌细胞和异种移植物增殖的特性。我们的目的是使用基于高通量液相色谱-质谱的方法研究白藜芦醇对 MCF-7 和 MDA-MB-231 人乳腺癌细胞系的作用所引起的代谢变化。在这两种细胞系中，生长抑制均呈剂量依赖性，并伴有明显的代谢变化。在白藜芦醇剂量为 100 μM 时，所有 21 种分析的氨基酸水平均增加了 100 倍以上，而 MDA-MB-231 细胞中的浓度远低于 MCF-7 细胞。在生物胺和修饰氨基酸（n=16）中，白藜芦醇在两种细胞系中使血清素、犬尿氨酸和亚精胺的合成增加了 61 倍，表明白藜芦醇与细胞生物胺代谢强烈相互作用。在类二十烷酸和氧化多不饱和脂肪酸（n=17）中，在 MDA-MB-231 细胞中观察到花生四烯酸及其代谢物 12S-HETE 明显增加，而在 MCF-7 细胞中则较少，表明在磷脂酶 A₂激活后从细胞膜磷脂释放，并随后由 12-脂氧合酶代谢。总之，代谢组学分析阐明了几种小分子作为乳腺癌细胞对白藜芦醇反应的标志物。
