Investigation of the cytotoxic effects of sertralin and capecitabin combination on breast cancer cells

Depression is defined as a common mood disorder that manifests itself simultaneously with chronic diseases. Especially in patients diagnosed with cancer, depression is commonly observed. In the case of neglectedness of depression treatment, the success of cancer treatment also decreases. According to gender-based studies, there are two-fold increase in depression prevalence in women than that of men. Besides this, breast cancer is the most common type of cancer in women. In this sense, the treatment of depression in women with breast cancer is very important for success in cancer treatment. Therefore, cancer patients undergoing chemotherapy in oncology units also use antidepressants simultaneously. At that point, it is very important to understand drug interactions used in combination correctly based on their detoxification mechanism similarity. This thesis is the first study in the literature investigating the in vitro cytotoxic effects of the combination of sertraline and capacitabine in human breast cancer cell lines (MCF7 and MDAMB-231). In this study it is indicated that capacitabine administration alone at doses of 1000-1.95 ng/ml was showed no cytotoxic effect at the end of 6-, 12- and 24-hour incubation periods while there was cytotoxic effect at 125 and 62.5 ng/mL doses at the end of 48 hours incubation period in MCF7 cells. Sertraline administration to MCF7 cells at the same doses did not show any cytotoxic effect at any dose and incubation period except 62.5 ng/ml at the end of the 24-hour incubation period. On MDAMB-231 cells, capacitabine did not show any cytotoxic effect at any dose but showed antiproliferative effect whereas sertraline had cytotoxic effect at all doses except 31.25 and 3.9 ng/mL at the end of the 6-hour incubation period, and at 125 ng/mL in the 24-hour incubation period. In addition, sertraline has an antiproliferative effect on MDAMB-231 cells at all doses and incubation times. Sertraline/capastabine combination reudced cell viability to 35.802% and 23.043% in MDAMB-231 and MCF7 cells, respectively. As a result, it is concluded that the sertraline/capacitabine combination reduced cell viability more than the seperate use of drugs. As a result of the obtained data; there is no statistically significant change in the amount of caspase-3,-8,-9 and DNA fragmentation in MDAMB-231 and MCF7 cells. Although it is not within the scope of the thesis, the amount of mtor protein was examined and it was determined that the amount of mtor was suppressed in both the cell extract and the supernatant when the drugs were used alone or in combination. It is found that the amount of mTOR is more suppressed in the cell supernatant than in the cell extract. The amount of mTOR was suppressed 0.717-fold at 100 ng/mL concentration of only capecitabine treated 0.757 fold at 50 ng/mL concentration of only sertraline treated and 0.525 fold in combinations from MDAMB-231 cells in the cell extract while 0.533 fold, 0.664 fold and 0.59 fold in the supernatant, respectively. On the other hand, in MCF7 cells the amount of mTOR in the cell extract was suppressed 0.045 fold at 10 ng/mL concentration of only capecitabine treated cells, 0.11 fold at 50 ng/mL concentration of only sertraline treated cells and 0.0612 fold in combinations whereas in the supernatant of the same cell line mTOR was suppressed as 0.8 fold, 0.725 fold and 0.775 fold, respectively. In the light of all these results, the absence of change in caspase-3,-8-9 and DNA fragmentation in cancer cells and the suppression of mTOR in both cell lines suggest that the death mechanism may be autophagy.