The Dicyano Compound Induces Autophagic or Apoptotic Cell Death Via Twıst/C-Myc Axis Depending on Metastatic Characteristics of Breast Cancer Cells

Abstract

\n Breast cancer is a heterogeneous disease which has distinct subtypes and therefore development of novel targeting treatments to fight aganist breast cancer is needed. Although autophagy and apoptosis considered as the major programmed cell death mechanisms are among the current target mechanisms, there are some difficulties in clinical treatment such as the development of drug resistance and cancer recurrence. Therefore it is important that illumination of distinctive mechanisms between cancer types for development novel treatment strategies. In this study, we examined the anti-proliferative effects of the triazole linked galactose substituted dicyano compound (hereafter referred to as the dicyano compound (the DC)) on two different breast cancer cell lines, MDA-MB-231 and MCF-7. We determined that response of each cell lines to the DC was different, since autophagy was induced in MDA-MB-231 and apoptosis was induced in MCF-7. For this reason, we hypothesized that these different responses may be due to the different characteristics of the cells and evaluated effects of aggresiveness degrees of both cell lines on response to the DC. As a result of our analysis, we determined that c-Myc regulation in both cell lines was different upon the DC treatment depending on expression of Twist, an epithelial-to-mesenchymal transition (EMT) mediator. Therefore, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in breast cancer subtypes.