Activation of autophagy promotes the inhibitory effect of curcumin analog EF‐24 against MDA‐MB‐231 cancer cells

Abstract

AbstractBreast cancer is the leading cause of cancer deaths in women worldwide. EF‐24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF‐24 against one breast cancer cell line, MDA‐MB‐231, and its anti‐migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF‐24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF‐24 also induced mitochondrial apoptosis in MDA‐MB‐231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3‐MA could reduce the cleavage of PARP protein and protect cells from EF‐24‐induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF‐24 in MDA‐MB‐231 cells, which suggest that EF‐24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF‐24 in breast cancer cells. Moreover, removal of EF‐24‐activated ROS with NAC significantly reversed migration ability of MDA‐MB‐231 cells, indicating that EF‐24 exerted an inhibitory effect through a ROS‐mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.