Berberine inhibits prostate cancer progression by inducing ferroptosis: evidence from network pharmacology

The uncertain ferroptosis-related role of berberine in prostate cancer was explored using network pharmacology methodology. Integration of ferroptosis targets in prostate cancer from the Genecard database and berberine targets from the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases revealed 17 common targets. Among these, 10 hub genes, including CCNB1, CDK1, AURKA, AR, CDC42, ICAM1, TYMS, NTRK1, PTGS2, and SCD, were identified. Enrichment analyses yielded 799 Gene Ontology terms and 23 Kyoto Encyclopedia of Genes and Genomes pathways associated with berberine-related targets. Molecular docking simulations indicated berberine's binding capacity to all hub genes. In-vitro studies on LNCaP and PC3 cells demonstrated berberine's inhibition of cell proliferation and significant downregulation of TYMS, CCNB1, AURKA, CDK1, and SCD in both cell lines. Berberine exhibited cell line-specific effects by reducing AR expression in LNCaP cells and suppressing ICAM1 in PC3 cells. Overall, berberine shows promise in inhibiting prostate cancer progression through modulation of ferroptosis-related genes, including TYMS, AR, CCNB1, AURKA, CDK1, ICAM1, NTRK1, SCD, and CDC42.