Anti-Breast Cancer Effects of Vitamin D3 Analogs Either Alone or in Combination with Other Agents
Abstract
We continue to pursue our in vitro and in vivo studies of novel vitamin D3 analogs used alone and in combination against breast cancer. We have altered our 19-nor analogs in an attempt to minimize hypercalcemic effects while retaining potency. We have synthesized a series of novel 20-cyclopropyl-cholecalciferol vitamin D3 analogs that were found to be potent inhibitors of clonal growth of MCF-7 breast cancer cells. We examined a new class of Vitamin D analogs that have a novel 5,6-trans motif. We examined the use of vitamin D analogs in combination with All-trans-retinoic acid in human breast tumors in BNX mice and found an additive effect which decreased tumor mass nearly 3-fold with minimal toxicity. Due to the dearth of in vivo studies examining the long term effects of Vitamin D analogs, we administered unique analogs for approximately one year to Balb/C mice and performed extensive toxicity analyses. We have found that Vitamin D analogs modulate BRCAI expression in breast cancer. We have initiated studies using the organic arsenical Melarsoprol (Mel-B)and All- trans-retinoic acid (ATRA) in human breast cancer cell lines and in human breast tumors in BNX mice and found significant apoptosis and a synergistic anti-cancer effect.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA362073
Entities
People
- Phillip Koeffler
Organizations
- Cedars-Sinai Medical Center