Abstract / Summary
Salvianolic acid A (SAA) exhibits antitumor activity against non-small cell lung cancer (NSCLC), but the metabolic regulatory mechanisms underlying its effects remain incompletely understood. In this study, we integrated desorption electrospray ionization mass spectrometry imaging (DESI-MSI), network pharmacology, molecular docking, and functional validation to investigate the effects of SAA on NSCLC. SAA inhibited H1299 cell viability, migration, and invasion and induced apoptosis. DESI-MSI analysis of xenograft tumor tissues revealed marked metabolic alterations after SAA treatment, including changes in ceramides, glycerophospholipids, and arachidonic acid candidates. Network pharmacology and molecular docking further suggested the involvement of oxidative stress- and apoptosis-related pathways. Functionally, SAA increased intracellular ROS levels, impaired mitochondrial function, and reduced mitochondrial membrane potential. Treatment with the ROS scavenger NAC partially reversed SAA-induced ROS accumulation, loss of cell viability, and increased levels of cleaved Caspase-9 and Caspase-3. Consistently, Western blotting and immunofluorescence analyses showed concentration-dependent activation of Caspase-9 and Caspase-3, whereas the pan-caspase inhibitor Z-VAD-FMK significantly attenuated SAA-induced cell death and apoptosis. Collectively, these findings provide evidence that SAA induces metabolic remodeling and promotes ROS-associated mitochondrial dysfunction and caspase-mediated apoptosis in NSCLC, thereby suggesting a potential metabolic mechanism underlying its antitumor activity.