Unité de Biochimie Hormonale et Nutritionnelle, Département de Biochimie, Toxicologie et Pharmacologie, Institut de Biologie et de Pathologie, Centre Hospitalier Universitaire de Grenoble, CS10217, 38043 Grenoble, France.
Biol Trace Elem Res. 2013 Aug;154(2):288-98. doi: 10.1007/s12011-013-9709-5. Epub 2013 Jun 16.
The beneficial effect of selenium (Se) on cancer is known to depend on the chemical form, the dose and the duration of the supplementation. The aim of this work was to explore long term antagonist (antioxidant versus toxic) effects of an inorganic (sodium selenite, Na2SeO3) and an organic (seleno-L-methionine, SeMet) forms in human immortalized keratinocytes HaCaT cells. HaCaT cells were supplemented with Na2SeO3 or SeMet at micromolar concentrations for 144 h, followed or not by UVA radiation. Se absorption, effects of UVA radiation, cell morphology, antioxidant profile, cell cycle processing, DNA fragmentation, cell death triggered and caspase-3 activity were determined. At non-toxic doses (10 μM SeMet and 1 μM Na2SeO3), SeMet was better absorbed than Na2SeO3. The protection of HaCaT from UVA-induced cell death was observed only with SeMet despite both forms increased glutathione peroxidase-1 (GPX1) activities and selenoprotein-1 (SEPW1) transcript expression. After UVA irradiation, malondialdehyde (MDA) and SH groups were not modulated whatever Se chemical form. At toxic doses (100 μM SeMet and 5 μM Na2SeO3), Na2SeO3 and SeMet inhibited cell proliferation associated with S-G2 blockage and DNA fragmentation leading to apoptosis caspase-3 dependant. SeMet only led to hydrogen peroxide production and to a decrease in mitochondrial transmembrane potential. Our study of the effects of selenium on HaCaT cells reaffirm the necessity to take into account the chemical form in experimental and intervention studies.
硒（Se）对癌症的有益作用取决于其化学形式、剂量和补充时间。本工作旨在探索无机（亚硒酸钠，Na2SeO3）和有机（硒代蛋氨酸，SeMet）两种形式的硒在人永生化角质形成细胞 HaCaT 中的长期拮抗剂（抗氧化剂与毒性）效应。HaCaT 细胞用 Na2SeO3 或 SeMet 在微摩尔浓度下培养 144 小时，随后或不进行 UVA 辐射。测定 Se 吸收、UVA 辐射的影响、细胞形态、抗氧化谱、细胞周期处理、DNA 片段化、细胞死亡触发和 caspase-3 活性。在非毒性剂量（10 μM SeMet 和 1 μM Na2SeO3）下，SeMet 的吸收优于 Na2SeO3。尽管两种形式均增加了谷胱甘肽过氧化物酶-1（GPX1）活性和硒蛋白-1（SEPW1）转录表达，但仅在用 SeMet 处理时，HaCaT 才受到保护，免受 UVA 诱导的细胞死亡。用 UVA 照射后，无论 Se 的化学形式如何，丙二醛（MDA）和 SH 基团均未发生变化。在毒性剂量（100 μM SeMet 和 5 μM Na2SeO3）下，Na2SeO3 和 SeMet 抑制细胞增殖，与 S-G2 阻滞和导致细胞凋亡 caspase-3 依赖性的 DNA 片段化相关。SeMet 仅导致过氧化氢的产生和线粒体跨膜电位的降低。我们对 HaCaT 细胞中硒作用的研究再次证实，在实验和干预研究中必须考虑到化学形式。
