Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Metallomics. 2011 Feb;3(2):162-8. doi: 10.1039/c0mt00091d. Epub 2010 Dec 16.
The aim of this work was to compare different selenium species for their ability to induce cell death in different cancer cell lines, while investigating the underlying chemistry by speciation analysis. A prostate cancer cell line (PC-3), a colon cancer cell line (HT-29) and a leukaemia cell line (Jurkat E6-1) were incubated with five selenium compounds representing inorganic as well as organic Se compounds in different oxidation states. Selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), methylseleninic acid (MeSeA), selenite and selenate in the concentration range 5-100 μM were incubated with cells for 24 h and the induction of cell death was measured using flow cytometry. The amounts of total selenium in cell medium, cell lysate and the insoluble fractions was determined by ICP-MS. Speciation analysis of cellular fractions was performed by reversed phase, anion exchange and size exclusion chromatography and ICP-MS detection. The selenium compounds exhibited large differences in their ability to induce cell death in the three cell lines and the susceptibilities of the cell lines were different. Full recovery of selenium in the cellular fractions was observed for all Se compounds except MeSeA. Speciation analysis showed that MeSeA was completely transformed during the incubations, while metabolic conversion of the other Se compounds was limited. Production of volatile dimethyl diselenide was observed for MeSeA and MeSeCys. MeSeA, MeSeCys and selenite showed noticeable protein binding. Correlations between cell death induction and the Se compounds transformations could not be demonstrated.
本研究旨在比较不同硒形态在诱导不同癌细胞系细胞死亡方面的能力，并通过形态分析研究其潜在的化学机制。我们培养了前列腺癌细胞系（PC-3）、结肠癌细胞系（HT-29）和白血病细胞系（Jurkat E6-1），并用代表不同氧化态的无机和有机硒化合物的五种硒化合物进行孵育。在浓度为 5-100 μM 的范围内，用硒代蛋氨酸（SeMet）、硒代蛋氨酸（MeSeCys）、甲基硒酸（MeSeA）、亚硒酸盐和硒酸盐孵育细胞 24 小时，并通过流式细胞术测量细胞死亡的诱导。用 ICP-MS 测定细胞培养基、细胞裂解物和不溶性部分中的总硒含量。通过反相、阴离子交换和尺寸排阻色谱和 ICP-MS 检测对细胞部分进行形态分析。五种硒化合物在三种细胞系中诱导细胞死亡的能力差异很大，细胞系的敏感性也不同。除了 MeSeA 之外，所有 Se 化合物在细胞部分的硒都得到了完全回收。形态分析表明，MeSeA 在孵育过程中完全转化，而其他 Se 化合物的代谢转化有限。观察到 MeSeA 和 MeSeCys 产生挥发性二甲基二硒。MeSeA、MeSeCys 和亚硒酸盐表现出明显的蛋白质结合。不能证明细胞死亡诱导与 Se 化合物转化之间存在相关性。
