Asaraldehyde suppresses non-small cell lung cancer progression via ferroptosis induction and inhibition of PI3K-AKT signaling.

Non-small cell lung cancer (NSCLC) is an aggressive malignancy characterized by poor therapeutic outcomes, and its progression is closely linked to dysregulated PI3K-AKT signaling and resistance to ferroptosis. This study aimed to investigate the anti-tumor effects of Asaraldehyde (Asa) on NSCLC, elucidate its underlying mechanisms, and explore its therapeutic potential by targeting both ferroptosis and the PI3K-AKT pathway. It was revealed that Asa treatment significantly suppressed NSCLC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) while inducing ferroptosis, as evidenced by increased lipid peroxidation, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion. Additionally, Asa promoted ubiquitin-mediated degradation of AKT, leading to inhibition of the PI3K-AKT signaling pathway, and this effect was partially attenuated by Ferrostatin-1, a ferroptosis inhibitor. In vivo, Asa administration significantly reduced tumor growth in a xenograft mouse model, accompanied by decreased expression of Ki67, AKT, and ferroptosis-related proteins. These findings demonstrate that Asa exerts potent anti-NSCLC activity through ferroptosis induction and PI3K-AKT pathway suppression, and suggest that targeting these pathways with Asa could provide a novel therapeutic strategy for NSCLC treatment.