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

Abstract

Background Breast cancer (BC) is a heterogeneous disease with various subtypes, therefore, the illumination of distinctive mechanisms between subtypes for the development of novel treatment strategies is important. Here, we revealed the antiproliferative effects of our customized dicyano compound (DC) on BC cells. Methods and results We determined the antiproliferative effect of the DC on non-metastatic MCF-7 and metastatic MDA-MB-231 cell lines by MTT. We evaluated protein levels of LC3BI-II and p62 to detect effects of the DC on autophagy. Furthermore, we examined whether the DC induce apoptosis in MCF-7 and MDA-MB-231 cells by performing TUNEL and western blotting. We showed that the DC induces autophagic cell death in MDA-MB-231 while it leads to apoptosis in MCF-7, demonstrating that DC can induce different cell death mechanisms in BC cells according to what they represent subtypes. To understand the reason of different cell response to the DC, we evaluated the expressions of several regulator proteins involved in survival, cell arrest and proliferation. All findings revealed that c-Myc expression is directly correlated with autophagy induction in BC cells and it could be a marker for the selection of cell death mechanism against anti-cancer drugs. Interestingly, we showed that the overexpression of Twist, responsible for metastatic features of BC cells, imitates the effects of autophagy on c-Myc expression in MCF-7 cells, indicating that it is implicated in both the regulation of c-Myc as a upstream factor and subsequently the selection of cell death mechanisms. Conclusion Taken together, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in BC subtypes with different invasive characteristics.