Berberine Synergizes with Cisplatin via Inducing Apoptosis on A549 non-Small Cell Lung Cancer Cells

Objective: Lung cancer is the most common cause of morbidity and mortality. Platinum-based chemotherapy, which is the primary line of treatment, offers limited benefit due to drug resistance and side effects. Berberine (BBR), which is characterised by its potent and safe anticancer activity, represents a promising combination option in chemotherapy. To overcome the limitations in lung cancer chemotherapy, we investigated whether BBR and cisplatin (CIS) exert synergistic effects on non-small cell lung cancer cell line (A549) based on cytotoxicity and apoptotic response markers. Methods: The potential cytotoxic effects of the combination treatment were evaluated using the MTT and Chou-Talalay methods. Elisa assays were also performed to measure the levels of the pro-apoptotic protein Bax and the effector protein caspase (Cas)-3. Results: The results showed that BBR alone reduced A549 cell viability in a dose-dependent manner and synergized with CIS (CI =0.34[+ or -]0.05 at IC50 concentrations). Elisa results showed that the combined treatment (both at IC50 concentrations) modulated apoptotic signalling pathways in A549 cells. Bax and Cas3 protein levels were dramatically enhanced in A549 cells treated with CIS +BBR compared to control (0.5% DMSO) (p < 0.001). Conclusion: Our results suggest that BBR can synergistically enhance the therapeutic effect of CIS in A549 cells. The potential therapeutic efficacy of BBR as part of a combination in current chemotherapy should be supported by in-depth research and clinical studies on the molecular mechanisms associated with cancer. Keywords: Berberine (BBR), Cisplatin (CIS), synergism, A549, apoptosis