Laboratory of Biochemistry, Department of Biological Applications & Technologies, University of Ioannina, 45110 Ioannina, Greece.
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Nutrients. 2019 Mar 7;11(3):574. doi: 10.3390/nu11030574.
Τhe effect of docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid) upon the proliferation of EoL-1 (Eosinophilic leukemia) cell line was assessed, while additional cellular events during the antiproliferative action were recorded. DHA inhibited EoL-1 cells growth dose-dependently by inducing growth arrest at G0/1 phase of the cell cycle. After DHA addition to the cells, the expression of oncogene was decreased, -mRNA overexpression was observed which was used as a marker of differentiation, and -mRNA increase was recorded. The enzymatic activities of phospholipase A₂ (PLA₂), a group of hydrolytic enzymes, whose action precedes and leads to PAF biosynthesis through the remodeling pathway, as well as platelet activating factor acetylhydrolase (PAFAH) which hydrolyses and deactivates PAF, were also measured. DHA had an effect on the levels of both the intracellular and secreted activities of PLA₂ and PAFAH. The inflammatory cytokines IL-6 and TNF-α were also detected in high levels. In conclusion, DHA-induced EoL-1 cells differentiation was correlated with downregulation of oncogene, overexpression of and -mRNAs, increase of the inflammatory cytokines production, and alteration of the enzymatic activities that regulate PAF levels. DHA is a natural substance and the understanding of its action on EoL-1 cells on molecular level could be useful in further investigation as a future therapeutic tool against F/P ⁺ hypereosinophilic syndrome.
二十二碳六烯酸（DHA，一种 ω-3 多不饱和脂肪酸）对 EoL-1（嗜酸性白血病）细胞系增殖的影响进行了评估，同时记录了抗增殖作用过程中的其他细胞事件。DHA 通过诱导细胞周期 G0/1 期生长停滞，呈剂量依赖性地抑制 EoL-1 细胞生长。DHA 添加到细胞后，癌基因的表达减少，观察到 -mRNA 的过表达，这被用作分化的标志物，并且记录到 -mRNA 的增加。还测量了磷脂酶 A₂（PLA₂）的酶活性，磷脂酶 A₂是一组水解酶，其作用通过重塑途径先于并导致 PAF 生物合成，以及血小板激活因子乙酰水解酶（PAFAH），其水解并使 PAF 失活。DHA 对 PLA₂ 和 PAFAH 的细胞内和分泌活性水平都有影响。还检测到高水平的炎症细胞因子 IL-6 和 TNF-α。总之，DHA 诱导的 EoL-1 细胞分化与下调癌基因、过表达 - 和 -mRNA、增加炎症细胞因子的产生以及调节 PAF 水平的酶活性的改变有关。DHA 是一种天然物质，了解其在 EoL-1 细胞上的作用在分子水平上可能有助于进一步研究作为对抗 F/P ⁺ 嗜酸性粒细胞增多症的未来治疗工具。
