Ursolic acid induces apoptosis in nasopharyngeal carcinoma cells through the P53 signaling pathway: a network pharmacology and experimental validation study.

Nasopharyngeal carcinoma (NPC) is a malignant neoplasm that is highly prevalent in East Asia and presents significant therapeutic challenges due to limited treatment options and severe adverse effects. Ursolic acid (UA) is a pentacyclic triterpenoid with anticancer activity in various tumors; however, its mechanism of action in NPC remains unclear. This study integrated network pharmacology with experimental validation to elucidate the molecular mechanism underlying the effect of UA against NPC. Screening of a network pharmacology database identified 39 targets common to UA and NPC, among which P53, STAT3, Bcl-2, IL1B, and CASP3 showed high node degrees in the protein-protein interaction network. Gene Ontology analysis revealed that these targets were primarily enriched in stress response and apoptosis regulation, whereas Kyoto Encyclopedia of Genes and Genomes analysis indicated significant enrichment in the P53 signaling and apoptosis pathways. UA dose-dependently inhibited the proliferation of the NPC cell lines S18 and S26 (p < 0.01), and induced apoptosis, as demonstrated by Annexin V-FITC/PI double fluorescence staining and confirmed by Hoechst 33,342 staining showing nuclear condensation. UA also caused mitochondrial membrane depolarization, as indicated by JC-1 staining. Western blot analysis showed significant upregulation of P53 and the pro-apoptotic protein BAX (p < 0.01), and downregulation of the anti-apoptotic protein Bcl-2 (p < 0.01) following UA treatment. This study is the first to show that UA induces apoptosis in NPC cells by activating the P53 signaling pathway using network pharmacology and experimental validation.