Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway

Abstract

// Dan Han 1, * , Gang Wu 1, * , Chan Chang 1 , Fang Zhu 1 , Yin Xiao 1 , Qiuhui Li 1 , Tao Zhang 1 , Liling Zhang 1 1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * These authors have contributed equally to this work Correspondence to: Liling Zhang, e-mail: lily-1228@hotmail.com Keywords: breast cancer, epithelial-mesenchymal transition, cancer stem cells, disulfiram Received: February 19, 2015      Accepted: September 20, 2015      Published: October 16, 2015 ABSTRACT Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway.