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Ellagic acid and human cancers: a systems pharmacology and docking study to identify principal hub genes and main mechanisms of action.
Molecular Diversity ( IF 3.9 ) Pub Date : 2020-05-14 , DOI: 10.1007/s11030-020-10101-6
Hamid Cheshomi 1 , Ahmad Reza Bahrami 1, 2, 3 , Maryam M Matin 1, 2, 3
Affiliation  

Research on anticancer properties of natural compounds, as effective materials that are available while causing minimal side effects, is growing. Ellagic acid (EA) is a well-known polyphenolic compound, which has been found in both free and complex modes in several medicinal plants such as pomegranate, walnut, and berries. Although many articles have reported anticancer properties for this compound, its mechanism of action has not been fully elucidated. In this study, we used several online and offline bioinformatics tools and databases to identify the mechanism of action of EA on various types of human malignancies including bladder, blood, breast, cervical, colorectal, liver, pancreas, and prostate cancers. In this context, after identifying and extracting EA-affected human genes/proteins that have been reported in various references, we built the related gene networks and determined functional hub genes. In addition, docking was performed to recognize target proteins that react directly with EA and are in fact most affected by this compound. Our findings revealed that EA exerts its anticancer effects by influencing specific hub genes in various types of cancers. Moreover, different cellular signaling pathways are affected by this natural compound. Generally, it turned out that EA probably exerts most of its anticancer activities, through induction of apoptosis, as well as P53 and WNT signaling pathways, and also by affecting the expression of several hub genes such as CDKN1A, CDK4, CDK2, CDK6, TP53, JUN, CCNA2, MAPK14, CDK1, and CCNB1 and especially interactions with some related proteins including P53, CDK6, and MAPK14.

中文翻译:

鞣花酸和人类癌症:一项系统药理学和对接研究,以确定主要枢纽基因和主要作用机制。

对天然化合物的抗癌特性的研究正在增长,因为天然化合物是可用的同时副作用最小的有效材料。鞣花酸 (EA) 是一种众所周知的多酚化合物,已在石榴、核桃和浆果等几种药用植物中以游离和复合模式被发现。尽管许多文章报道了该化合物的抗癌特性,但其作用机制尚未完全阐明。在这项研究中,我们使用了几个在线和离线生物信息学工具和数据库来确定 EA 对各种类型的人类恶性肿瘤的作用机制,包括膀胱癌、血液癌、乳腺癌、宫颈癌、结肠直肠癌、肝癌、胰腺癌和前列腺癌。在这种情况下,在识别和提取各种参考文献中报道的受 EA 影响的人类基因/蛋白质后,我们建立了相关的基因网络并确定了功能枢纽基因。此外,进行对接以识别直接与 EA 反应且实际上受该化合物影响最大的靶蛋白。我们的研究结果表明,EA 通过影响各种癌症中的特定中枢基因来发挥其抗癌作用。此外,不同的细胞信号通路受这种天然化合物的影响。一般而言,结果表明 EA 可能通过诱导细胞凋亡以及 P53 和 WNT 信号通路发挥其大部分抗癌活性,还通过影响 CDKN1A、CDK4、CDK2、CDK6、TP53 等几个中枢基因的表达、JUN、CCNA2、MAPK14、CDK1 和 CCNB1,尤其是与一些相关蛋白(包括 P53、CDK6 和 MAPK14)的相互作用。
更新日期:2020-05-14
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