Ferroptosis-like cell death induced by Amomi Fructus phenolic compounds in SGC7901 gastric cancer cells: a network pharmacology and experimental validation study.

BACKGROUND

To investigate the mechanism of Amomi Fructus phenolic compounds (AFPC) induced ferroptosis-like cell death in gastric cancer (GC) using a multiomics strategy combining network pharmacology, molecular dynamics simulations (MDS), and experimental validation.

METHODS

Potential targets of AFPC, ferroptosis, and GC were systematically analyzed via network pharmacology, protein-protein interaction (PPI) analysis, molecular docking, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, multi-omics databases (UALCAN, GEPIA, Kaplan-Meier Plotter, HPA, and TISCH1), MDS, and in vitro experiments on SGC7901 cells.

RESULTS

Two potential candidate bioactive compounds (gallic acid and quercetin) and five predicted central signaling nodes (TP53, HIF1A, IL-6, STAT3, and EGFR) were identified, among which only the IL-6/STAT3 pathway was experimentally validated. GO and KEGG analyses indicated that AFPC treatment in GC primarily involves oxidative stress, nuclear localization, p53 binding, and cancer-associated pathways. Molecular docking and simulations suggested that gallic acid and quercetin may act through modulating these predicted central signaling nodes. AFPC triggered ferroptosis by elevating Fe²+/malondialdehyde (MDA) and depleting glutathione (GSH), suppressing IL-6/STAT3 signaling, and inhibiting SGC7901 cell viability in a dose-dependent manner.

CONCLUSIONS

AFPC triggers ferroptosis-like cell death and inhibits GC progression associated with IL-6/STAT3 pathway inhibition, with gallic acid and quercetin as potential bioactive components, suggesting a plausible GC therapeutic strategy and the utility of multi-disciplinary approaches in herbal medicine mechanism research.