Combined Effect of Sertraline and Capecitabine on Breast Cancer Cell Lines In Vitro and In Silico Evidence for Synergistic Interaction

Background: Depression is a common mood disorder that manifests itself simultaneously with chronic diseases. It is especially common in patients diagnosed with cancer, and when neglected, it reduces the success of cancer treatment. The fact that breast cancer is the most common type of cancer in women shows that the treatment of depression in women with cancer is very important. As a result, cancer patients undergoing chemotherapy in oncology units also use antidepressants simultaneously. It is critical to correctly understand the interactions between drugs used in combination. Method: In this study, doses were prepared for MCF7 and MDAMB-231 cell lines by serial dilution from 1000 ng/mL to 1.95 ng/mL. Cell viability was calculated with the WST-1 kit by applying the prepared doses of capecitabine and sertraline alone. In the sertraline/capecitabine combination study, cell viability was examined in MDAMB-231 and MCF-7 cells by applying doses of 300, 100, 50, 25, 10 ng/mL. Combinations that showed selective cytotoxicity after the combination were analyzed with the CompuSyn program and the combination index (CI<1 = synergism) was calculated. Studies on caspase 3-8-9, DNA fragmentation and mTOR were continued using a combination that showed a synergistic effect. Result: It was determined that compared to drug use alone, the sertraline/capecitabine combination decreased cell viability. There is no significant difference in caspase-3,-8,-9 and DNA fragmentation in cancer cells, but there is a reduction in the level of mTOR. This suggests that the death mechanism may be autophagy. Docking studies with autophagy pathway-related proteins further support our results. It is noteworthy that the AKT1-sertraline complex had the best binding affinity among the target proteins (-9.1 kcal/mol).