1.20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis.
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
Acta Pharmaceutica Sinica B 2020;10(6):1020-1035
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 used a comprehensive single-cell 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 proteome-metabolome 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()-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.
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