Original articles
Zhihua Wang, Wenbo Wu, Xiangchen Guan, Shuang Guo, Chaowen Li, Ruixue Niu, Jie Gao, Min Jiang, Liping Bai, Elaine Laihan Leung, Yuanyuan Hou, Zhihong Jiang, Gang Bai. 20(S)-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network via multiomic analysis[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 1020-1035

20(S)-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network via multiomic analysis
Zhihua Wanga, Wenbo Wua, Xiangchen Guana, Shuang Guoa, Chaowen Lia, Ruixue Niua, Jie Gaoa, Min Jianga, Liping Baib, Elaine Laihan Leungb, Yuanyuan Houa, Zhihong Jiangb, Gang Baia
a State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China;
b State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, China
Abstract:
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks.Here, we useda comprehensive singlecell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteomemetabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20(S)-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.
Key words:    Multiomics analysis    P53    20(S)-Protopanaxatriol    DNA binding    Ginsenosides anti-tumor network   
Received: 2019-09-01     Revised: 2019-12-02
DOI: 10.1016/j.apsb.2020.01.017
Funds: This research was supported by International Cooperation and Exchange of the National Natural Science Foundation of China (No. 81761168039), Macau Science and Technology Development 345 Fund (No. 015/2017/AFJ, China), and National Key Research and Development Program of China (Nos. 2018YFC1704800 and 2018YFC1704805).
Corresponding author: Yuanyuan Hou, Zhihong Jiang, Gang Bai     Email:houyy@nankai.edu.cn;zhjiang@must.edu.mo;gangbai@nankai.edu.cn
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Authors
Zhihua Wang
Wenbo Wu
Xiangchen Guan
Shuang Guo
Chaowen Li
Ruixue Niu
Jie Gao
Min Jiang
Liping Bai
Elaine Laihan Leung
Yuanyuan Hou
Zhihong Jiang
Gang Bai

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