1 A-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent
Abstract
Recently we identified a novel vitamin D analog, la-hydroxy-24 ethyl vitamin D5 (1alpha(OH)D5) that showed potent growth inhibitory and cell-differentiating actions in breast cancer cells. Based on our findings in in vitro and in vivo experimental model systems, we hypothesized that 1 alpha(OH)D5, when administered to women with breast cancer, will induce differentiation of dedifferentiated cells and thereby prevent progression of malignancy. The major tasks proposed for 1999-2000 are 1) perform preclinical toxicity study of la(OH)D5 according to GLP; 2) determine in vitro effect of la(OH)D5 on normal and malignant breast tissues; 3) prepare 1 alpha(OH)D5 according to GMP for future phase I clinical trial. We completed the preclinical study in rats. Our results show that 1 alpha(OH)D5 has no serious toxicity; a hypercalcemic effect was observed at high dose, which was reversible. In vitro study in tissues obtained from patients show that 1 alpha(OH)D5 has no effect on normal breast epithelial cells, but it induces apoptosis in breast cancer. It also showed apoptotic effect in fibroadenomas. We have completed 5 steps in the synthesis of 1 alpha(OH)D5 for preparation of 1 alpha(OH)D5 for phase I clinical study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA385273
Entities
People
- Tapas D. Gupta
Organizations
- University of Illinois at Chicago