Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans
Emodin, a natural inhibitor of protein kinase CK2, suppresses growth, hyphal development, and biofilm formation of Candida albicans
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DOI：
10.1002/yea.3230
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发表时间：
2017-06-01
期刊：
影响因子：
2.6
通讯作者：
Golczyk, Hieronim
中科院分区：
文献类型：
--
作者：
Janeczko, Monika;Maslyk, Maciej;Golczyk, Hieronim
大黄素（1，3，8-三羟基-6-甲基蒽醌）是一种天然次生植物产物，最初从掌叶大黄（Rheumpalmatum）的根茎中分离得到。许多研究表明其具有利尿、舒张血管、抗菌、抗病毒、抗溃疡、免疫抑制、保肝、抗炎和抗癌等作用。大黄素是一种多效性分子，能够与几种主要的分子靶点相互作用。G. NF-κ B、AKT/mTOR和STAT 3。该化合物还可以作为一些蛋白激酶的抑制剂，对蛋白激酶CK 2具有特殊的亲和力。本报告的目的是评价大黄素的抗真菌特性及其对从念珠菌细胞中分离的CK 2的活性。我们的研究表明，该化合物抑制参考菌株以及临床念珠菌菌株的细胞生长，最小抑制浓度和最小杀真菌浓度值在12.5和200 μ g/mL之间。此外，在低浓度下，该化合物能够有效地阻止菌丝形成，从而显示出明显的抗毒性潜力。有趣的是，我们发现大黄素加入到念珠菌培养物中抑制了许多细胞蛋白的磷酸化，这可能是由于抑制了蛋白激酶CK 2。值得注意的是，从念珠菌细胞中分离的酶对大黄素敏感，IC 50为2.8 μ g/mL。事实上，我们的计算模型显示，大黄素能够占据CK 2的ATP结合口袋。版权所有（C）2017约翰威利父子有限公司
Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural secondary plant product, originally isolated from the rhizomes of Rheum palmatum. Many reports show its diuretic, vasorelaxant, antibacterial, antiviral, anti-ulcerogenic, immunosuppressive, hepatoprotective, anti-inflammatory and anticancer potential. Emodin is a pleiotropic molecule capable of interacting with several major molecular targets, e. g. NF-kappa B, AKT/mTOR and STAT3. The compound can also act as an inhibitor of some protein kinases, with special affinity to protein kinase CK2. The aim of the presented report was to evaluate antifungal properties of emodin and its activity towards CK2 isolated from Candida cells. Our studies revealed that the compound suppressed growth of the cells of reference strains as well as clinical Candida strains, with minimal inhibitory concentration and minimal fungicidal concentration values between 12.5 and 200 mu g/mL. Moreover, at a low concentration, the compound was able to effectively stop hyphal formation, thus showing a distinct antivirulent potential. Interestingly, we showed that emodin added to Candida culture inhibited the phosphorylation of many cellular proteins, presumably owing to the inhibition of protein kinase CK2. Notably, the enzyme isolated from the Candida cells was susceptible to emodin with IC50 of 2.8 mu g/mL. Indeed, our computational modelling revealed that emodin was able to occupy the ATP-binding pocket of CK2. Copyright (C) 2017 John Wiley & Sons, Ltd.