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来自黄粘盖牛肝菌的异松塔牛肝菌素可诱导K562细胞系的细胞周期停滞和凋亡。

Iso-suillin from the mushroom Suillus flavus induces cell cycle arrest and apoptosis in K562 cell line.

作者信息

Wang Ying, Zhang Qingshuang, Zhao Junxia, Zhao Xiaojing, Zhang Jinxiu, Wang Li-an

机构信息

College of Life Sciences, Hebei Normal University, No. 20, Road East of 2nd Ring South, Yuhua District, Shijiazhuang 050024, China.

The Basic Medical College, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China.

出版信息

Food Chem Toxicol. 2014 May;67:17-25. doi: 10.1016/j.fct.2014.02.007. Epub 2014 Feb 14.

Abstract

Iso-suillin, an isomer of suillin that belongs to the prenylphenol class of fungal derivatives, was isolated from petroleum ether extracts of Suillus flavus. The IC50 value of iso-suillin in K562 cells was 0.87 μM, which was lower than the positive control cisplatin (19.33 μM). Iso-suillin-treated K562 cells exhibited an increased rate of apoptosis, mitochondrial membrane potential (MMP) depolarization, and G0/G1 arrest. Western blot analysis revealed that these cells displayed significantly upregulated expression of several apoptosis-related proteins, including cytochrome c, caspase 9, FADD (Fas-associating protein with a novel death domain), caspase 8, caspase 3, and Bax. Moreover, the expression of two anti-apoptosis proteins, NF-κB and Bcl-2, was downregulated. Inhibitors of caspase 9 and caspase 8 protected the K562 cells from apoptosis. Taken together, our results suggest that iso-suillin induces K562 apoptosis through the mitochondrial and death receptor pathways and that iso-suillin may represent a candidate anti-leukemia treatment.

摘要

异松覃酮是松覃酮的异构体,属于真菌衍生物的异戊烯基苯酚类,它是从黄粘盖牛肝菌的石油醚提取物中分离出来的。异松覃酮在K562细胞中的IC50值为0.87μM,低于阳性对照顺铂(19.33μM)。经异松覃酮处理的K562细胞凋亡率增加、线粒体膜电位(MMP)去极化以及细胞周期停滞于G0/G1期。蛋白质免疫印迹分析表明,这些细胞中几种凋亡相关蛋白的表达显著上调,包括细胞色素c、半胱天冬酶9、FADD(具有新死亡结构域的Fas相关蛋白)、半胱天冬酶8、半胱天冬酶3和Bax。此外,两种抗凋亡蛋白NF-κB和Bcl-2的表达下调。半胱天冬酶9和半胱天冬酶8的抑制剂可保护K562细胞免于凋亡。综上所述,我们的结果表明异松覃酮通过线粒体和死亡受体途径诱导K562细胞凋亡,并且异松覃酮可能是一种抗白血病治疗的候选药物。

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