<p>ABSTRACT</p><p>Background: Breast cancer is the most frequently diagnosed type of cancer and is the second leading cause of cancer-related death in women. Objective: In this study, it was aimed to evaluate the histological and genetic responses of different breast cancer cell lines (MCF-7 and MDA-MB-231) to adiponectin exposure in cell culture medium. Methods: BrdU and immunohistochemical staining was performed with Caspase-3, TLR3, TLR4 on two-dimensional breast cancer cell cultures. Histological differences were investigated by gene expression method. Results: In immunohistochemical staining experiments with caspase-3; It was determined that in the adiponectin groups administered 100-250-500 ng, more cells were labeled with caspase-3 at all hours compared to the control group. At the end of the</p><p>immunohistochemical study with TRL3/4; It was determined that more cells were marked with TLR3/4 at all doses and at all hours in the adiponectin applied groups compared to the control group. According to the gene expression findings, AdipoR1 gene expression levels were found to be statistically significant in the MCF-7 cell line, where the AdipoR1 gene expression level increased due to the increased adiponectin concentration. Adiponectin application in MDA-MB 231 cell line was found to be statistically significant only at the 48th hour, only 250 ng/mL. Discussion and Conclusion: In our study, we identified adiponectin as a new growth inhibitor of MCF-7 and MDA-MB-231 breast cancer cells. We also investigated, for the first time, the immunohistochemical effects of adiponectin TLR3/4 in MCF-7 and MDA-MB-231 cell lines. In conclusion, we suggest that the increase in TLR3/4 expression of adiponectin in both MCF- 7 and MDA-MB-231 cell lines is due to the increase in DAMP with concentration-dependent increasing apoptosis.</p>