A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells
A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells
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富硒灵芝中的一种新型多糖诱导人乳腺癌细胞凋亡
DOI：
10.3892/or_00001070
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发表时间：
2011-01-01
期刊：
影响因子：
4.2
通讯作者：
Fu, Xin
中科院分区：
文献类型：
--
作者：
Shang, Dejing;Li, Yang;Fu, Xin
从富硒灵芝中分离得到的新型多糖SeGLP-2B-1在体外对多种癌细胞具有抗增殖活性。为了探讨其抗肿瘤机制，我们研究了SeGLP-2B-1在人乳腺癌细胞中的凋亡作用，并进一步阐明了其作用机制。Annexin V/PI染色检测细胞凋亡。采用Caspase凋亡检测试剂盒检测Caspase活性。Western blot法检测procaspase-3、-8、-9、PARP和细胞色素c的表达水平。结果显示，SeGLP-2B-1抑制MCF-7细胞生长呈时间和剂量依赖性。观察到细胞凋亡的典型特征，包括形态学改变、亚g1细胞和DNA阶梯形成。进一步分析表明，SeGLP-2B-1处理破坏了线粒体膜电位，随后细胞色素c细胞质水平升高。随后，SeGLP-2B-1以时间依赖性的方式增加caspase-9、-3和聚ADPribose聚合酶的活性，但未观察到caspase-8的明显激活。Caspase-9和caspase-3抑制剂可阻止SeGLP-2B-1诱导的细胞凋亡，且SeGLP-2B-1可显著上调caspase-3、-9的活性。我们的研究表明，SeGLP-2B-1通过线粒体介导的途径诱导细胞凋亡。
The novel polysaccharide SeGLP-2B-1 isolated from Se-enriched Ganoderma lucidum, showed antiproliferative activity towards several cancer cell lines in vitro. To investigate the antitumor mechanisms, the apoptotic effects of SeGLP-2B-1 in human breast cancer cells were studied, and the mechanism of this action was further elucidated. Cell apoptosis was detected by Annexin V/PI staining. Caspase activity was assayed using a caspase apoptosis detection kit. Western blot analysis was used to evaluate the levels of procaspase-3, -8, -9, PARP and cytochrome c expression. The results showed that SeGLP-2B-1 inhibited the growth of MCF-7 cells in a time- and dose-dependent manner. Typical characteristics of apoptosis were observed, including morphological changes, sub-G 1 cells and DNA ladder formation. Further analysis showed that SeGLP-2B-1 treatment disrupted the mitochondrial membrane potential followed by an increase in the cytochrome c cytosolic levels. Sequentially, SeGLP-2B-1 increased the activities of caspase-9, -3 and poly (ADPribose) polymerase in a time-dependent manner, however, no obvious activation of caspase-8 was observed. Caspase-9 and caspase-3 inhibitor prevented SeGLP-2B-1-induced apoptosis, and the activities of caspases-3, -9 were significantly upregulated by SeGLP-2B-1. Our studies suggest that SeGLP-2B-1 induces apoptosis via a mitochondria-mediated pathway.