Forkhead transcription factor FoxMl represents a promising therapeutic target as it is seen to be upregulated in numerous human malignancies including breast cancer, but it is not expressed in non-dividing normal cells. We identified two thiazole antibiotics, Siomycin A and structurally related thiostrepton as novel inhibitors of FoxMl. We showed previously that thiazole antibiotics act as proteasome inhibitors, efficiently down-regulate FoxMl expression and induce potent apoptosis in various cancer cells. In this study, we explored the potential anticancer properties of Simoycin A and thiostrepton against human breast cancer in culture and in a mouse model of breast cancer. We found that thiazole antibiotics inhibit the growth of multiple human breast cancer cell lines in low micromo-lar concentrations, the protein expression of FoxMl and also induce cell death in these cancer cells. In addition, we showed for the first time that thiazole antibiotics inhibit tumor growth in vivo, in a xeno-graft model of human breast cancer.
展开▼
