Curcumin inhibits the growth via Wnt/beta-catenin pathway in non-small-cell lung cancer cells

OBJECTIVE: In recent decades, the death rate from lung cancer appears to be an increasing yearly trend, particularly for non-small-cell lung cancer (NSCLC). Curcumin is a yellow pigment found in turmeric rhizomes. reported to exhibit various anti-inflammatory, anti-angiogenic, anti-proliferative, and antioxidant properties. Many reports have suggested that curcumin could induce apoptosis in malignant cells, and therefore, has great potential in tumor treatment. However, little is known about the effect of curcumin on NSCLC or its associated mode of action. Therefore, in this study. we explored curcumin's effect on NSCLC and investigated its associated mechanism. MATERIALS AND METHODS: The non-small-cell lung cancer (NSCLC) cell line A549 was cultured and subjected to MTT and clonogenic survival assays to assess cell proliferation. Reactive oxygen species (ROS) levels were measured using a Fluostar Omega Spectrofluorimeter. Superoxide dismutase (SOD) and gamma-glutamyl cysteine synthetase (gamma-GCS) activity in A549 cells were both determined by a commercial determination kit. Expression levels of p-GSK3 beta (Ser9), c-Myc, cyclin D1, beta-catenin alpha-tubulin, and proliferating cell nuclear antigen (PCNA) were analyzed by Western blot. RESULTS: Results of the MTT and clonogenic survival assay indicated that curcumin reduced A549 proliferation. ROS levels and SOD and gamma-GCS activities were detected. Curcumin decreased intracellular ROS levels and increased SOD and gamma-GCS activity. Meanwhile, the ROS inhibitor N-Acetylcysteine (NAC) reversed the decrease in ROS levels and the increase in SOD and gamma-GCS activity. These results indicate that oxidative stress is involved in the curcumin-induced reduction of A549 viability. Curcumin also strongly inhibited beta-catenin and p-GSK3 beta (Ser9) protein expression, as well as the expres- sion of downstream cyclin D1 and c-Myc. Similarly, NAC reversed the inhibition of beta-catenin and p-GSK3 beta (Ser9) protein expression, as well as the expression of downstream cyclin D1 and c-Myc. CONCLUSIONS: We showed that curcumin inhibits NSCLC proliferation via the Wnt/beta-catenin pathway.