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Steroid Receptor Coactivator-3 (SRC-3/AIB1) as a Novel Therapeutic Target in Triple Negative Breast Cancer and Its Inhibition with a Phospho-Bufalin Prodrug.
- Source :
-
PloS one [PLoS One] 2015 Oct 02; Vol. 10 (10), pp. e0140011. Date of Electronic Publication: 2015 Oct 02 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Triple negative breast cancer (TNBC) has the poorest prognosis of all types of breast cancer and currently lacks efficient targeted therapy. Chemotherapy is the traditional standard-of-care for TNBC, but is frequently accompanied by severe side effects. Despite the fact that high expression of steroid receptor coactivator 3 (SRC-3) is correlated with poor survival in estrogen receptor positive breast cancer patients, its role in TNBC has not been extensively investigated. Here, we show that high expression of SRC-3 correlates with both poor overall survival and post progression survival in TNBC patients, suggesting that SRC-3 can serve as a prognostic marker for TNBC. Furthermore, we demonstrated that bufalin, a SRC-3 small molecule inhibitor, when introduced even at nM concentrations, can significantly reduce TNBC cell viability and motility. However, because bufalin has minimal water solubility, its in vivo application is limited. Therefore, we developed a water soluble prodrug, 3-phospho-bufalin, to facilitate its in vivo administration. In addition, we demonstrated that 3-phospho-bufalin can effectively inhibit tumor growth in an orthotopic TNBC mouse model, suggesting its potential application as a targeted therapy for TNBC treatment.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation drug effects
Cell Survival drug effects
Female
Humans
Mice
Mice, Inbred ICR
Mice, SCID
Receptors, Estrogen metabolism
Bufanolides pharmacology
Nuclear Receptor Coactivator 3 metabolism
Prodrugs pharmacology
Triple Negative Breast Neoplasms drug therapy
Triple Negative Breast Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26431029
- Full Text :
- https://doi.org/10.1371/journal.pone.0140011