Huang Chao, Ba Qian, Yue Qingxi, Li Junyang, Li Jingquan, Chu Ruiai, Wang Hui
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Mol Biosyst. 2013 Dec;9(12):3091-100. doi: 10.1039/c3mb70342h. Epub 2013 Oct 2.
Artemisinin and related compounds (artemisinins), as a frontline treatment for malaria, have been used to save millions of lives. Their potential application in cancer treatment is promising. Nevertheless, the precise mechanisms of action of artemisinins are still controversial. In particular, the system-level influence of artemisinins on protein interactions and regulatory networks remains unknown, limiting progress in development of this class of compounds as anticancer drugs. In the present study, we investigated the mechanism of action of artemisinins in cancer therapy through an analysis based on biological networks. According to experimental evidence from more than 400 literature studies, 558 key proteins were derived and the artemisinins-rewired protein interaction network was constructed. Topological properties were analyzed to show that the protein network was a scale-free biological system. And the modularity analysis and pathway identification were performed. Five key pathways including PI3K-Akt, T cell receptor, Toll-like receptor, TGF-beta and insulin signaling pathways were involved in artemisinins-mediated anticancer effects; their identification was confirmed by microarray data. Based on these results, predictions were made about the targets of artemisinins in various pathways. These results provide a deeper understanding of the molecular mechanisms of action of artemisinins and will contribute to the development and application of this class of compounds in cancer treatment.
青蒿素及相关化合物（青蒿素类）作为疟疾的一线治疗药物，已挽救了数百万人的生命。它们在癌症治疗中的潜在应用前景广阔。然而，青蒿素类的确切作用机制仍存在争议。特别是，青蒿素类对蛋白质相互作用和调控网络的系统层面影响尚不清楚，这限制了这类化合物作为抗癌药物的开发进展。在本研究中，我们通过基于生物网络的分析来探究青蒿素类在癌症治疗中的作用机制。根据400多篇文献研究的实验证据，推导得出558个关键蛋白，并构建了青蒿素类重塑的蛋白质相互作用网络。分析拓扑性质表明该蛋白质网络是一个无标度生物系统。并进行了模块性分析和通路鉴定。PI3K-Akt、T细胞受体、Toll样受体、TGF-β和胰岛素信号通路这五条关键通路参与了青蒿素类介导的抗癌作用；微阵列数据证实了它们的鉴定。基于这些结果，对青蒿素类在各种通路中的靶点进行了预测。这些结果为深入了解青蒿素类的分子作用机制提供了依据，并将有助于这类化合物在癌症治疗中的开发和应用。
