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共轭亚麻酸异构体紫铆酸对人嗜酸性粒细胞白血病EoL-1细胞的凋亡诱导及分化诱导活性

Apoptosis- and differentiation-inducing activities of jacaric acid, a conjugated linolenic acid isomer, on human eosinophilic leukemia EoL-1 cells.

作者信息

Liu Wai-Nam, Leung Kwok-Nam

机构信息

Biochemistry Programme, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.

出版信息

Oncol Rep. 2014 Nov;32(5):1881-8. doi: 10.3892/or.2014.3446. Epub 2014 Aug 26.

Abstract

Conjugated linolenic acids (CLNAs) are a group of naturally occurring positional and geometrical isomers of the C18 polyunsaturated essential fatty acid, linolenic acid (LNA), with three conjugated double bonds (C18:3). Although previous research has demonstrated the growth-inhibitory effects of CLNA on a wide variety of cancer cell lines in vitro, their action mechanisms and therapeutic potential on human myeloid leukemia cells remain poorly understood. In the present study, we found that jacaric acid (8Z,10E,12Z-octadecatrienoic acid), a CLNA isomer which is present in jacaranda seed oil, inhibited the in vitro growth of human eosinophilic leukemia EoL-1 cells in a time- and concentration-dependent manner. Mechanistic studies showed that jacaric acid triggered cell cycle arrest of EoL-1 cells at the G0/G1 phase and induced apoptosis of the EoL-1 cells, as measured by the Cell Death Detection ELISAPLUS kit, Annexin V assay and JC-1 dye staining. Notably, the jacaric acid-treated EoL-1 cells also underwent differentiation as revealed by morphological and phenotypic analysis. Collectively, our results demonstrated the capability of jacaric acid to inhibit the growth of EoL-1 cells in vitro through triggering cell cycle arrest and by inducing apoptosis and differentiation of the leukemia cells. Therefore, jacaric acid might be developed as a potential candidate for the treatment of certain forms of myeloid leukemia with minimal toxicity and few side effects.

摘要

共轭亚麻酸(CLNAs)是C18多不饱和必需脂肪酸亚麻酸(LNA)的一组天然存在的位置和几何异构体,含有三个共轭双键(C18:3)。尽管先前的研究已证明CLNA在体外对多种癌细胞系具有生长抑制作用,但其对人髓系白血病细胞的作用机制和治疗潜力仍知之甚少。在本研究中,我们发现存在于蓝花楹籽油中的CLNA异构体紫铆酸(8Z,10E,12Z-十八碳三烯酸)以时间和浓度依赖性方式抑制人嗜酸性粒细胞白血病EoL-1细胞的体外生长。机制研究表明,紫铆酸触发EoL-1细胞在G0/G1期的细胞周期停滞,并诱导EoL-1细胞凋亡,这通过细胞死亡检测ELISAPLUS试剂盒、膜联蛋白V测定和JC-1染料染色来测量。值得注意的是,形态学和表型分析显示,经紫铆酸处理的EoL-1细胞也发生了分化。总体而言,我们的结果证明了紫铆酸通过触发细胞周期停滞以及诱导白血病细胞凋亡和分化来抑制EoL-1细胞体外生长的能力。因此,紫铆酸可能被开发成为治疗某些形式髓系白血病的潜在候选药物,具有最小的毒性和很少的副作用。

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