Exploring the mechanism of piperlongumine in promoting ferroptosis in cervical cancer based on network pharmacology and molecular docking analysis

Cervical cancer is the fourth most common cancer in women, characterized by a high incidence. Piperlongumine, a bioactive alkaloid derived from Piper longum , exhibits diverse biological activities. This study aimed to investigate the effects of piperlongumine on cervical cancer and elucidate its underlying mechanisms. Cell viability, proliferative potential, and migratory ability were evaluated using the cell counting kit-8 (CCK-8) assay, colony formation assays, and transwell assays, respectively. Malondialdehyde (MDA) and ferrous ion (Fe 2 + ) levels were measured with specific kits, while reactive oxygen species (ROS) levels were detected via flow cytometry. The SwissTargetPrediction, SuperPred, and Genecards databases were employed to predict potential targets. A protein-protein interaction (PPI) network was constructed on the STRING website, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of these targets conducted using DAVID. Molecular docking analysis between piperlongumine and protein targets was performed using AutoDockTools software. Piperlongumine suppressed cervical cancer cell viability, proliferation, and migration while inducing ferroptosis. A total of 33 common targets linked to cervical cancer ferroptosis and piperlongumine were identified. The analysis indicated significant enrichment of these targets in cancer-related lipid metabolism and diabetes complication pathways, along with Th17 cell differentiation and the HIF-1 signaling pathway. Notably, HIF1α, HSP90AA1, and MTOR among the common targets were confirmed to form stable bindings with piperlongumine. Piperlongumine promotes ferroptosis in cervical cancer cells by binding to HIF1α, HSP90AA1, and MTOR implicated in cervical cancer ferroptosis. These findings provide novel insights for the development of therapeutic strategies against cervical cancer.