The Role of VDR Phosphorylation in Vitamin D-Induced Apoptosis
Abstract
Vitamin D3 compounds are currently in clinical trials for human breast cancer and offer an alternative approach to anti-hormonal therapies for this disease. 1 ,25-Dihydroxyvitamin D3 (1 ,25-(OH)2 D(3)), the active form of vitamin D3, induces apoptosis in breast cancer cells and tumors, but the underlying mechanisms are poorly characterized. In these studies, we focused on the role of caspase activation and mitochondrial disruption in 1,25- (OH)2 D(3) mediated apoptosis in MCF-7 breast cancer cells in vitro. The effect of 1 ,25-(OH)2 D(3) on MCF-7 cells was compared to that of tumor necrosis factor a (TNF alpha), which induces apoptosis via a caspase-dependent pathway. Our major findings are that 1,25-(OH)2 D(3) induces apoptosis in MCF-7 cells by disruption of mitochondrial function which is associated with Bax translocation to mitochondria, cytochrome C release, and production of reactive oxygen species.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA388510
Entities
People
- Carmen J. Narvaez
- JoEllen Welsh
Organizations
- University of Notre Dame