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.
Keywords: breast cancer; cancer stem cells; disulfiram; epithelial-mesenchymal transition.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Alcohol Deterrents / pharmacology
- Animals
- Apoptosis / drug effects
- Blotting, Western
- Breast Neoplasms / etiology
- Breast Neoplasms / metabolism
- Breast Neoplasms / pathology
- Breast Neoplasms / prevention & control*
- Cell Cycle / drug effects
- Cell Movement / drug effects
- Cell Proliferation / drug effects
- Disulfiram / pharmacology*
- Electrophoretic Mobility Shift Assay
- Epithelial-Mesenchymal Transition / drug effects*
- Female
- Fluorescent Antibody Technique
- Humans
- Immunoenzyme Techniques
- MAP Kinase Signaling System / drug effects*
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- NF-kappa B / metabolism*
- Neoplastic Stem Cells / drug effects*
- Neoplastic Stem Cells / metabolism
- Neoplastic Stem Cells / pathology
- Snail Family Transcription Factors
- Transcription Factors / metabolism*
- Transforming Growth Factor beta / pharmacology*
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
Substances
- Alcohol Deterrents
- NF-kappa B
- Snail Family Transcription Factors
- Transcription Factors
- Transforming Growth Factor beta
- Disulfiram