Evaluation of cytotoxic and apoptotic effects of Tamoxifen - DEBİO 1143 combination on estrogen receptor positive breast cancer cell culture

Breast cancer is one of the most common and deadly cancer type among the women in the world. Tamoxifen (TAM), which is a selective estrogen modulator (SERM) is the most fovoured anti-hormone therapy for breast cancer. Combination therapies are being developed against developing resistance due to long time usage of TAM in the estrogen receptor positive (ER+) breast cancer and to increase the efficacy of treatment. Various SMAC mimetics which function as antagonists of the endogenous IAP protein family have drawn great attention as new cancer agents in treatment of different types of cancer in recent years. In this study, it is aimed to be revealed cytotoxic effect of using TAM and DEBIO 1143 as single agents and combined agents with increasing concentrations in MCF-7 and BT-474 ER+ breast cancer cell lines. Concentrations applied at 48th and 72th hours. Results are achieved by using XTT cytotoxicity test. To determine cytotoxic effect and which type of cell death to associate with, multi parameter apoptosis assay has been performed. The obtained data were analyzed by using one-way analysis of variance test (ANOVA) and Dunnet's statistical test. According to XTT test results IC50 value of TAM has been detected as 3.8 ± 0.6 μM, 18.9 ± 6.7 μM in MCF-7 and BT-474 cells, respectively. However IC50 value of DEBIO 1143 has been detected only in MCF-7 cells as 15 ± 0.5 μM. DEBİO 1143 agent's low cytotoxic effect has been detected only for 20 μM in BT-474 cells. According to our combination data, it has been observed that there is a synergistic effect to all of combination doses in both cell lines. Our combination results obtained were found statistically significant according to ANOVA and Dunnet`s analysis for both cell lines (p<0.001). It is showed that the cytotoxic effect of combination was not associated with apoptosis, might be related to the other types of cell death. As a result, cytotoxic effect of combination doses in ER+ cells, compared to single application of TAM and DEBİO 1143 has synergistic effect. It is concluded that advanced researches are needed to be performed to determine cytotoxic effect of combined treatment might be associated with which type of cell death mechanism except for apoptosis.