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(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.

尽管已知肿瘤抑制物P53调节广泛的信号通路网络，但仍不清楚某些药物如何影响这些P53信号网络。在这里，我们使用了人参皂甙对癌细胞影响的综合单细胞多组学观点。转录组和蛋白质组分析表明，人参皂甙的抗肿瘤活性与P53蛋白密切相关。miRNA-蛋白质组相互作用网络显示P53控制至少38种蛋白质的转录，蛋白质组代谢组分析显示蛋白质P53调控蛋白质参与核苷酸代谢，氨基酸代谢和“ Warburg效应”。综合多组学分析的结果表明，P53蛋白是影响人参皂苷抗肿瘤活性的潜在关键靶标。此外，S）-protopanaxatriol直接靶向P53 DNA结合口袋的相邻区域，并促进P53-DNA相互作用的稳定性，从而进一步引起了一系列的组学变化。