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

ABSTRACT: Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-?B. NF-?B 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-? to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-? 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-?B was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-?B activity and downregulate ERK/NF-?B/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-?B/Snail pathway.

SUBMITTER: Han D 

PROVIDER: S-EPMC4747377 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature