Quinaldic Acid Inhibits A549 Lung Cancer Cell Growth Through S-Phase Accumulation and Apoptosis

Myxobacteria are prolific producers of structurally diverse secondary metabolites and represent a valuable source of anticancer lead compounds. In this study, quinaldic acid (QA) was putatively annotated from a myxobacterial metabolite extract by LC–MS/MS spectral matching and evaluated for its antitumor activity against non-small cell lung cancer (NSCLC) cells. QA inhibited the viability of four tumor cell lines in a concentration-dependent manner, with A549 lung adenocarcinoma cells displaying the highest sensitivity, with an IC50 of 1.07 mM after 24 h of treatment. QA also significantly suppressed clonogenic growth in A549 cells. Network pharmacology analysis suggested that QA may regulate NSCLC-related targets and pathways involved in cell-cycle control, apoptosis, p53, JAK–STAT, and NF-κB signaling. Experimental validation showed that QA induced S-phase accumulation in A549 cells, increasing the S-phase population by 14.70 percentage points at 4 mM. This effect was accompanied by increased cyclin A1 expression and decreased cyclin B1 and CDK1 expression. QA also promoted apoptosis in a concentration-dependent manner, increasing the apoptotic population by 40.40 percentage points at 2 mM. Apoptosis was associated with elevated BAX and caspase-3 expression and reduced BCL-2 expression. These findings suggest that QA suppresses A549 cell growth by inducing S-Phase accumulation and apoptosis, supporting its potential as a myxobacteria-derived anticancer scaffold.