Combined Effects of Curcumin and Carboplatin on Mitochondrial Depolarization and Caspase Activation in Human Lung Adenocarcinoma Cells.

Background: In various kinds of cancer, including Non-Small Cell Lung Cancer (NSCLC), treatment resistance diminishes the effectiveness of current therapeutic approaches and underscores the need for new treatment strategies.

Aim: This study aimed to investigate the combined and individual effects of the anticancer drug carboplatin and the natural antioxidant curcumin, as well as the apoptotic effects of these drugs on the A549 cancer cells.

Objectives: The synergistic effect of the combined treatment with curcumin and carboplatin on lung cancer cells was evaluated, focusing on early apoptosis, caspase-3/9 activity, and mitochondrial membrane potential.

Methods: The cytotoxic effects were determined using the MTT method. Apoptotic changes were examined using the Annexin V-FITC labeling method. Activation of caspases-9 and -3 and mitochondrial membrane potential were measured using flow cytometry.

Results: The IC50 values of curcumin and carboplatin against A549 cells were determined to be 60±8 μM and 100±9 μM, respectively. The combination of curcumin and carboplatin showed a synergistic effect. After treating A549 cells with carboplatin, curcumin, or the combined use of curcumin+carboplatin for 12 hours, the rates of early apoptotic cells were determined to be 9.5±1.3%, 8.1±0.3%, and 22.2±2.9%, respectively. The rate of early apoptosis in combined use was significantly higher compared to individual use. Similarly, when the combined treatment of curcumin and carboplatin was compared to the administration of carboplatin alone, a higher level of mitochondrial membrane depolarization was observed. There was a slight increase in caspase 9 activity in the combined treatment group compared to the individual treatments. Furthermore, after treating A549 cells with the specified doses, the caspase 3 activity was determined for carboplatin (0.5±0.1%), curcumin (1.9±0.0%), and the combination of both (7.3±0.8%).

Conclusion: These results indicated that the combined use of curcumin and carboplatin enhanced apoptosis and mitochondrial depolarization, demonstrating that the combined treatment of drugs reduced the toxic dose of carboplatin. However, further research is needed to comprehensively understand the potential of this effect in in vivo studies.