ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells.
ROS-dependent mitochondria molecular mechanisms underlying antitumor activity of Pleurotus abalonus acidic polysaccharides in human breast cancer MCF-7 cells.
复制标题
鲍鱼菇酸性多糖在人乳腺癌 MCF-7 细胞中抗肿瘤活性的 ROS 依赖性线粒体分子机制
DOI：
10.1371/journal.pone.0064266
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Shi X;Zhao Y;Jiao Y;Shi T;Yang X
研究背景：食用富含真菌多糖的蘑菇可以大大降低患癌症的风险，这一点已被普遍接受。同时，可食用鲍鱼菇作为鲍鱼菇家族的一员，是一种受欢迎的营养补充剂，据称可以预防癌症的发生。然而，这些轶事索赔支持有限的研究描述肿瘤抑制反应的有前途的多糖，这些特性的分子机制尚未阐明。方法/主要发现我们在此将鲍鱼鲍子实体的粗多糖制剂分级分离成三个级分，即PAP-1、PAP-2和PAP-3，并测试这些级分在人乳腺癌MCF-7细胞中的抗增殖活性。最大的PAP-3是一种酸性多糖组分，分子量为3.68×105 Da，对MCF-7癌细胞的抑制活性最高，IC 50为193 µg/mL。DAPI染色观察细胞正常形态的变化，Annexin V/propidium iodide染色证实PAP-3诱导的细胞凋亡。细胞凋亡主要通过线粒体膜电位（Δ Km）降低、Bax/Bcl-2比值升高、caspase-9/3激活、聚腺苷二磷酸核糖聚合酶（PARP）降解以及细胞内活性氧（ROS）产生等途径实现。PAP-3还诱导p53上调，并使细胞周期停滞在S期。用抗氧化剂超氧化物歧化酶（SOD）和N-乙酰半胱氨酸（NAC）孵育MCF-7细胞显著减弱了PAP-3引起的ROS产生和凋亡，表明细胞内ROS在细胞死亡中起关键作用。这些发现表明多糖，特别是酸性PAP-3，是非常重要的营养成分，至少部分地负责鲍鱼通过ROS介导的线粒体凋亡途径的抗癌健康益处。这是一项重大突破，为多糖作为保健食品或药物的潜在用途带来了新的见解，为人类癌症提供了重要的天然防御。
Background A greater reduction in cancer risk associated with mushroom diet rich in fungus polysaccharides is generally accepted. Meanwhile, edible Pleurotus abalonus as a member of Abalone mushroom family is a popular nutritional supplement that purportedly prevents cancer occurrence. However, these anecdotal claims are supported by limited studies describing tumor-inhibitory responses to the promising polysaccharides, and the molecular mechanisms underlying these properties have not yet been elucidated. Methodology/Principal Findings We here fractionated the crude polysaccharide preparation from the fruiting bodies of P. abalonus into three fractions, namely PAP-1, PAP-2 and PAP-3, and tested these fractions for antiproliferative activity in human breast cancer MCF-7 cells. The largest PAP-3, an acidic polysaccharide fraction with a molecular mass of 3.68×105 Da, was the most active in inhibiting MCF-7 cancer cells with an IC50 of 193 µg/mL. The changes in cell normal morphology were observed by DAPI staining and the PAP-3-induced apoptosis was confirmed by annexin V/propidium iodide staining. The apoptosis was involved in mitochondria-mediated pathway including the loss of mitochondrial membrane potential (Δψm), the increase of Bax/Bcl-2 ratio, caspase-9/3 activation, and poly(ADP-ribose) polymerase (PARP) degradation, as well as intracellular ROS production. PAP-3 also induced up-regulation of p53, and cell cycle arrest at the S phase. The incubation of MCF-7 cells with antioxidant superoxide dismutase (SOD) and N-acetylcysteine (NAC) significantly attenuated the ROS generation and apoptosis caused by PAP-3, indicating that intracellular ROS plays a pivotal role in cell death. Conclusions/Significance These findings suggest that the polysaccharides, especially acidic PAP-3, are very important nutritional ingredients responsible for, at least in part, the anticancer health benefits of P. abalonus via ROS-mediated mitochondrial apoptotic pathway. It is a major breakthrough bringing new insight of the potential use of the polysaccharides as health-care food or medicine to provide significant natural defense against human cancer.
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影响因子：
11.2
作者：
Gan, Dan;Ma, Liping;Zeng, Xiaoxiong
通讯作者：
Zeng, Xiaoxiong
影响因子：
4.8
作者：
Ahmed, MM;Alcock, A;Freeman, JW
通讯作者：
Freeman, JW
影响因子：
4.8
作者：
Maity, Pallab;Bindu, Samik;Bandyopadhyay, Uday
通讯作者：
Bandyopadhyay, Uday
影响因子：
56.9
作者：
Marzo, I;Brenner, C;Kroemer, G
通讯作者：
Kroemer, G
影响因子：
8.8
作者：
Manzi, P;Gambelli, L;Pizzoferrato, L
通讯作者：
Pizzoferrato, L