Ethnopharmacological relevance: Tripterygium wilfordii Hook. f. (TW) is extensively utilized in clinical practice for its effective anti-inflammatory and anti-cancer properties.
Aim of the study: This study aims to elucidate the processes of TW in combating prostate cancer through a comprehensive strategy that integrates network pharmacology, molecular docking and molecular biology validation.
Materials and methods: A drug-target network and protein-protein interaction network were constructed established to predict the potential targets of TW for prostate cancer treatment. The interaction between active components and targets was confirmed using molecular docking. Moreover, prostate cancer cells were used to examine the anti-tumor effects of active ingredients in vitro. The xenograft animal model was constructed to evaluate the anti-tumor effect of triptonoterpene in vivo.
Results: Twenty-nine active components interact with 226 corresponding targets, and 112 disease targets specifically related with prostate cancer were identified. The primary targets (AKT1, TP53, RELA) were chosen, and kaempferol, triptolide, and triptonoterpene exhibited probable binding affinity with these targets, respectively. Triptonoterpene was subsequently confirmed to inhibit the growth of prostate cancer cells and induce apoptosis in vitro and in vivo.
Conclusion: Overall, this study demonstrated that TW may serve as a viable therapeutic agent for prostate cancer. Triptonoterpene is a specific inhibitor of p-AKT1 and p65, making it an attractive contender for prostate cancer therapy.
Keywords: Molecular docking; Network pharmacology; Prostate cancer; Tripterygium wilfordii Hook. f.; Triptonoterpene.
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