Back to Search
Start Over
Evaluation of C-2-substituted 19-nor-1alpha,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer.
- Source :
-
The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2007 Mar; Vol. 103 (3-5), pp. 717-20. Date of Electronic Publication: 2007 Jan 04. - Publication Year :
- 2007
-
Abstract
- 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) is known to inhibit the proliferation and invasiveness of prostate cancer cells. However, 1alpha,25(OH)(2)D(3) can cause hypercalcemia and is not suitable as a therapeutic agent. 19-Nor-vitamin D derivatives are known to be less calcemic when administered systemically. In order to develop more potent anti-cancer agents with less calcemic side effect, we therefore utilized (3)H-thymidine incorporation as an index for cell proliferation and examined the antiproliferative activities of nine C-2-substituted 19-nor-1alpha,25(OH)(2)D(3) analogs in the immortalized PZ-HPV-7 normal prostate cell line. Among the nine analogs we observed that the substitution with 2alpha- or 2beta-hydroxypropyl group produced two analogs having antiproliferative potency that is approximately 500- to 1000-fold higher than 1alpha,25(OH)(2)D(3). The (3)H-thymidine incorporation data were supported by the cell counting data after cells were treated with 1alpha,25(OH)(2)D(3), 19-nor-2alpha-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) or 19-nor-2beta-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) for 7 days. 19-Nor-2alpha-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) and 19-nor-2beta-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) were also shown to be about 10-fold more active than 1alpha,25(OH)(2)D(3) in cell invasion studies using prostate cancer cells. In conclusion, a substitution at the C-2 position of 19-nor-1alpha,25(OH)(2)D(3) molecule with a hydroxypropyl group greatly increased the antiproliferative and anti-invasion potencies. Thus, these two analogs could be developed to be effective therapeutic agents for treating early and late stages of prostate cancer.
Details
- Language :
- English
- ISSN :
- 0960-0760
- Volume :
- 103
- Issue :
- 3-5
- Database :
- MEDLINE
- Journal :
- The Journal of steroid biochemistry and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 17207993
- Full Text :
- https://doi.org/10.1016/j.jsbmb.2006.12.009