Ginseng glucosyl oleanolate inhibited ATP production and induced ferroptosis in non-small cell lung cancer

This study aimed to investigate the effect of ginseng glucosyl oleanolate (GGO) on non-small cell lung cancer (NSCLC) both in vitro and in vivo. GGO significantly inhibited the proliferation of A549 cells and tumor growth of A549-xenograft nude mice. Metabonomics analysis showed that GGO treatment changed the metabolites of glycolysis and tricarboxylic acid (TCA) cycle, which was consistent with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of transcriptomics. GGO inhibited the expression of glutaminase (GLS), decreased the content of glutamic acid and the carbon input of the TCA cycle, and finally significantly blocked the production of ATP. Meanwhile, GGO treatment decreased the levels of glutathione (GSH) and glutathione peroxidase (GPX), increased the accumulation of Fe²⁺ and malondialdehyde (MDA), downregulated solute carrier family 7 member 11 (SLC7A11) and GPX4 protein expression, which led to the redox imbalance and induced ferroptosis in A549 cells and tumor tissue. These findings provided compelling evidence that GGO may represent a potential new approach to treating NSCLC.