20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis.
- Author:
Zhihua WANG
1
;
Wenbo WU
1
;
Xiangchen GUAN
1
;
Shuang GUO
1
;
Chaowen LI
1
;
Ruixue NIU
1
;
Jie GAO
1
;
Min JIANG
1
;
Liping BAI
2
;
Elaine Laihan LEUNG
2
;
Yuanyuan HOU
1
;
Zhihong JIANG
2
;
Gang BAI
1
Author Information
- Publication Type:Journal Article
- Keywords: 20(S)-Protopanaxatriol; DNA binding; Ginsenosides anti-tumor network; Multiomics analysis; P53
- From: Acta Pharmaceutica Sinica B 2020;10(6):1020-1035
- CountryChina
- Language:English
- 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 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.