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鸡油菌分枝甘露聚糖通过干扰 NF-κB 通路信号转导抑制结肠癌细胞生长。

Cantharellus cibarius branched mannans inhibits colon cancer cells growth by interfering with signals transduction in NF-ĸB pathway.

机构信息

Department of Medical Biology, Institute of Rural Health, Lublin, Poland.

CQ-Vila Real, Chemistry Research Centre, Chemistry Department, Food and Wine Chemistry Lab., University of Trás-os-Montes e Alto Douro, Vila Real, Portugal.

出版信息

Int J Biol Macromol. 2019 Aug 1;134:770-780. doi: 10.1016/j.ijbiomac.2019.05.072. Epub 2019 May 15.

DOI:10.1016/j.ijbiomac.2019.05.072
PMID:31100403
Abstract

In order to evaluate the therapeutic potential of polysaccharides obtained from the widely consumed Cantharellus cibarius mushroom on NF-ĸB pathway involved in cancer cells proliferation, survival, and metastasis, their antiproliferative and cytotoxic properties in human colon cancer cells LS180 and human colon epithelial cells CCD841 CoN were studied. BrdU and LDH assays results show that a branched mannan isolated from C. cibarius (CC2a) was selective against colon cancer cells, suppressing their proliferation and destroying membrane integrity but at the same time not adversely affecting colon epithelial cells. Results of Western blotting, immunofluorescence, RealTime PCR revealed that CC2a anticancer abilities were accompanied by disorders in signals transduction in NF-ĸB pathway in particular inhibition of IκBα degradation, attenuation of activated NF-κB phosphorylation and the subsequent decrease of NF-κB nuclear level as well as significant down-regulation of NF-κB target genes BAX, BCL2, CCND1, MMP9, MYC, BIRC5 and the corresponding proteins (except Bax). Furthermore, CC2a treatment of LS180 cells resulted in perturbation in G0/G and S phases of the cell cycle also associated with a marked increase of DNA fragmentation as well as inhibition of cancer cells motility. Obtained results indicated C. cibarius branched mannans as a new option in fighting with colon cancer.

摘要

为了评估广泛食用的鸡油菌中多糖对参与癌细胞增殖、存活和转移的 NF-ĸB 通路的治疗潜力,研究了其对人结肠癌细胞 LS180 和人结肠上皮细胞 CCD841 CoN 的增殖抑制和细胞毒性作用。BrdU 和 LDH 检测结果表明,从鸡油菌(CC2a)中分离出的支链甘露聚糖对结肠癌细胞具有选择性,抑制其增殖并破坏细胞膜完整性,但同时不会对结肠上皮细胞产生不利影响。Western blot、免疫荧光和 RealTime PCR 结果表明,CC2a 的抗癌能力伴随着 NF-ĸB 通路信号转导的紊乱,特别是抑制 IκBα降解、减弱激活的 NF-κB 磷酸化以及随后 NF-κB 核水平的降低,以及 NF-κB 靶基因 BAX、BCL2、CCND1、MMP9、MYC、BIRC5 和相应蛋白(除 Bax 外)的显著下调。此外,CC2a 处理 LS180 细胞导致细胞周期的 G0/G1 和 S 期出现紊乱,同时伴随着 DNA 片段化的显著增加和癌细胞运动的抑制。研究结果表明,鸡油菌支链甘露聚糖是对抗结肠癌的一种新选择。

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