The investigation of the anti-tumoral effect of debi̇o-1143 on triple negative mouse breast cancer cell lines

Breast cancer is a common type of cancer among women. In triple negative breast cancer (Triple Negative Breast Cancer-TNBC), which is one of the subtypes, the expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) are absent. Because of these properties, TNBC is lacking in therapeutic targets and the response to treatment is very low. In this thesis study, it was aimed to investigate the cytotoxic effect of DEBIO 1143, which is a SMAC mimetic, in triple negative type 4T1 and 4T1-HER2 (+) mouse breast cancer cell lines and through which cell death pathway this effect occurs. In the study, MTT test was used to determine cell viability, flow cytometry analysis was performed to determine apoptosis, and fluorescence microscopy was used to determine autophagy from MDC staining results. According to MTT test, DEBIO 1143 IC50 dose was found as 20.49 µM and 36.2 µM in 24 and 48 hour 4T1 cell lines, respectively. It was determined as 19.56 µM and 22.45 µM in 24 and 48 hour 4T1 HER2 (+) cell lines, respectively. Cell viability results obtained from flow cytometry analysis were 96.7% and 98.1%, respectively, in 4T1 and 4T1 HER2 (+) cell lines treated with DEBIO 11434 for 24 hours. When the results of the application groups were compared with the control group (99.6% and 99.6%, respectively), it was determined that there was no significant percentage difference between them. When the results obtained from the 48-hour drug administered group in both cell lines were compared with the control groups, it was determined that DEBIO 1143 IC50 doses caused cell death. In the 4T1 cell line, DEBIO 1143 caused 0.8% early apoptosis, 3.6% late apoptosis and 43.7% non-apoptotic cell death. It was determined that DEBIO 1143 IC50 dose applied to 4T1 HER2 (+) breast cancer cells caused 3.4% early apoptotic, 4.8% late apoptotic and 27.1% non-apoptotic cell death. On the other hand, 99.7% cell viability was determined in the control group. According to MDC staining results, it was determined that DEBIO 1143 application significantly increased the number of vesicles in both cell lines. According to the findings, DEBIO 1143 showed a time-dependent cytotoxic effect in triple negative mouse breast cancer cell lines, indicating that this effect is mediated by non-apoptosis cell death mechanisms.