Vitamin D3 Mediated Tumor Regression.
Abstract
1,25(OH)2D3 and its synthetic analog EB 1089 induce characteristic features of apoptosis in MCF-7 cells in vitro. To determine whether vitamin D3 compounds could mediate apoptosis of breast tumors in vivo, we treated nude mice carrying MCF-7 xenografts with the vitamin D3 analog EB1089 for up to five weeks. The volume of tumors from mice treated with 45 pmol/ day EB1089 was four-fold lower than that of tumors from vehicle treated control mice after five weeks. The reduced growth of tumors from EB 1089 treated mice was associated with characteristic apoptotic morphology. After five weeks of treatment with EB 1089, MCF-7 tumors exhibited a six-fold increase in DNA fragmentation and a two-fold reduction in proliferation relative to control tumors. EB 1089 treatment did not alter the growth of xenografts derived from a vitamin D3 resistant variant of MCF-7 cells (McF%7D3Res cells), which display resistance to EB1089 in vifro, indicating that resistance to EB 1089 is maintained in vivo. Failure of current endocrine therapies for breast cancer has been attributed to the emergence of hormone independent cells, suggesting that agents like EB 1089 which induce apoptosis in both ER+ (estrogen receptor) and ER- cells represent promising adjuncts to existing therapies for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA358074
Entities
People
- Kathryn Van Weelden
Organizations
- The W. Alton Jones Cell Science Center