Resveratrol induces ferroptosis to repress malignant progression of lung cancer cells

Lung cancer (LC) is a highly lethal malignancy arising from tracheobronchial mucosal or glandular epithelium, responsible for ~18% of global cancer mortality, with poor long‑term patient survival. Resveratrol (Res, 445154), a natural polyphenol enriched in grapes, peanuts and Polygonum cuspidatum, exhibits robust anti‑inflammatory and antioxidant effects. Since chronic inflammation promotes tumorigenesis, Res may restrain tumor progression via disrupting inflammatory cascades. This study aimed to evaluate Res‑mediated suppression of proliferation, migration and invasion in LC cells, and delineate its roles in inducing apoptosis and ferroptosis. MTT, trypan blue exclusion and colony formation assays were used to assess the anti‑proliferative effects of Res. Wound healing, Transwell migration and Matrigel invasion assays together with western blotting were performed to examine LC cell migration, invasion and related molecular mechanisms. Differentially expressed genes were screened from the Gene Expression Omnibus (GEO) datasets, followed by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict the potential cell death pathways modulated by Res. DCFH‑DA staining, JC‑1 assay, glutathione quantification, western blotting and ferrostatin‑1 rescue experiments were performed to confirm Res‑triggered ferroptosis. Functional experiments showed that Res markedly suppressed LC cell proliferation, migration and invasion via the epithelial‑mesenchymal transition pathway and induced apoptosis. Bioinformatics analysis identified enrichment of the arachidonic acid metabolism pathway in Res‑treated cells. Owing to the close link between arachidonic acid metabolism and ferroptosis, we hypothesized that Res triggers ferroptosis in LC cells, which was verified by cellular assays. In summary, Res exerts broad anti‑tumor effects in LC cells by restraining proliferation, migration and invasion and stimulating apoptosis and ferroptosis.