Investigating Scopoletin as a Potential Anti-cancer Agent Targeting the AKT1/mTOR Pathway in A549 Lung Cancer Cells

Background Lung cancer is a notorious disease due to its high malignancy and complex metabolic adaptations, often regulated by the Akt/mTOR pathway. Purpose This study investigates the anti-cancer potential of scopoletin, a naturally derived bioactive compound, on A549 lung cancer cells, focusing on its effects on cancer cell viability and metabolic state. Materials and Methods A549 cells treated with scopoletin were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and morphological analysis to evaluate cytotoxic effects. Dual staining and metabolic assays analyzed apoptosis induction and metabolic shifts, including lipid peroxidation and antioxidant enzyme (superoxide dismutase (SOD) and catalase (CAT)) activity. Real-time polymer chain reaction (RT-PCR) confirmed gene expression changes, and molecular docking using AutoDock evaluated scopoletin binding affinity to key targets within the Akt/mTOR-mediated pathways. Additionally, colony formation and cell migration assays demonstrated scopoletin’s ability to suppress lung cancer malignancy. Results Our results showed that scopoletin effectively stops A549 cell proliferation through apoptosis and disrupts aerobic glycolysis, a characteristic feature of lung cancer’s metabolic state. RT-PCR results showed the downregulation of genes associated with glycolysis and apoptosis, consistent with the observed cellular effects. Furthermore, scopoletin inhibited colony formation and cell migration, indicating its potential to limit lung metastasis. Docking studies confirmed the strong binding interactions between scopoletin and targets within the Akt/mTOR signaling pathway, suggesting a mechanism by which scopoletin modulates lung cancer cell metabolism. Conclusion These findings indicate scopoletin’s potential to inhibit A549 cell growth and induce significant metabolic alterations, making it a viable therapeutic candidate for lung cancer. Further research is required to substantiate scopoletin clinical applicability and enhance therapeutic approaches for lung malignancies.