Cardamonin inhibited cell viability and tumorigenesis partially through blockade of testes-specific protease 50-mediated nuclear factor-kappaB signaling pathway activation
Cardamonin inhibited cell viability and tumorigenesis partially through blockade of testes-specific protease 50-mediated nuclear factor-kappaB signaling pathway activation
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小豆蔻苷部分通过阻断睾丸特异性蛋白酶 50 介导的核因子-kappaB 信号通路激活来抑制细胞活力和肿瘤发生
DOI：
10.1016/j.biocel.2016.02.001
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发表时间：
2016-04-01
影响因子：
4
通讯作者：
Li, Yu-Xin
中科院分区：
文献类型：
--
作者：
Mi, Xu-Guang;Song, Zhen-Bo;Li, Yu-Xin
已有研究表明，TSP50是一种在多种肿瘤中过表达的原癌基因，可促进细胞增殖、侵袭、肿瘤发生和肿瘤转移，是一种潜在的药物治疗靶点。本文利用TSP50基因启动子驱动的荧光素酶检测系统筛选TSP50的表达抑制物。研究发现，豆蔻素是一种黄酮类化合物，可以从mRNA和蛋白水平有效地抑制TSP50的表达。进一步的结果表明，豆蔻宁还通过诱导G2/M期停滞和线粒体依赖性的细胞凋亡，有效地抑制了TSP50高表达癌细胞的活力。令人惊讶的是，下调TSP50基因的表达与豆蔻碱治疗效果相同。此外，还发现豆蔻甲素对体内高表达TSP50的肿瘤生长有抑制作用。相反，TSP50的过表达显著降低了细胞对豆蔻碱抑制作用的敏感性，并逆转了豆蔻碱抑瘤作用的减弱。此外，TSP50干预和豆蔻宁处理均可抑制p65核转位，TSP50的过表达可逆转豆蔻宁对p65核转位的抑制作用。综上所述，这些结果表明豆蔻甲素至少部分通过阻断TSP50介导的核因子-kappaB信号通路的激活来抑制细胞的存活和肿瘤的发生，豆蔻甲素可能是一种有前途的抗癌药物候选药物，用于开发一种新的TSP50高表达癌细胞的药物。(C)2016爱思唯尔有限公司。保留所有权利。
Previous studies have shown that testes-specific protease 50 (TSP50), a pro-oncogene overexpressed in many types of tumors, could promote cell proliferation, invasion, tumorigenesis, and tumor metastasis, suggesting that it is a potential cancer therapeutic target in drug discovery. Here, a luciferase assay system driven by the TSP50 gene promoter was used to screen the inhibitor of expression of TSP50. The study found that cardamonin, a flavone compound, could efficiently inhibit the expression of TSP50 in both mRNA and protein levels. Further results revealed that cardamonin also efficiently inhibited the viability of TSP50 high-expressing cancer cells by inducing G2/M-phase arrest and mitochondrialdependent apoptosis. Surprisingly, knocking down the expression of TSP50 gene had the same effects as treatment with cardamonin. Moreover, it has been found that cardamonin had an inhibitory potency on TSP50 high-expressing tumor growth in vivo. In contrast, overexpression of TSP50 greatly decreased the cell sensitivity to the inhibitory effect of cardamonin and reversed the decreased tumor-inhibitory effect of cardamonin. Additionally, both TSP50 interference and treatment with cardamonin could suppress p65 nuclear translocation, and overexpression of TSP50 reversed the suppressive effect of cardamonin on p65 nuclear translocation. Taken together, these results suggest that cardamonin inhibited cell viability and tumorigenesis at least partially via blocking the activation of TSP50-mediated nuclear factor-kappaB signaling pathway, and cardamonin may be a promising anticancer drug candidate in the development of a novel agent for TSP50 high-expressing cancer cells. (C) 2016 Elsevier Ltd. All rights reserved.