ISSN:
0730-2312
Keywords:
vitamin D3 analogs
;
24-oxo metabolites
;
growth inhibition
;
differentiation
;
apoptosis
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
The seco-steroid hormone, 1α,25 dihydroxyvitamin D3 (1α,25(OH)2D3) binds to a specific nuclear receptor that acts as a ligand-inducible transcription factor. The resulting genomic effects include partial arrest in G0/G1 of the cell cycle and induction of differentiation; these effects have been observed in various types of cancer. Recently, we produced enzymatically the natural 24-oxo metabolites of 1α,25(OH)2D3 and two of its potent synthetic analogs (1α,25-(OH)2-16-ene-D3 and 1α,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1α,25(OH)2D3 and its analogs have either the same or greater antiproliferative activity against various cancer cells as their parental compounds. Notably, two cell lines (DU-145 (prostate cancer) and MDA-MB-436 [breast cancer]) that were extremely resistant to the antiproliferative effects of vitamin D3 analogs displayed greater sensitivity towards the 24-oxo metabolite of the vitamin D3 analog. Similarly, the 24-oxo metabolites had the capacity to induce differentiation and apoptosis and to diminish the proportion of cells in S phase. Most interestingly, while the analog 1α,25(OH)2-20-epi-D3 induced expression of BRCA1 in MCF-7 breast cancer cells; its 24-oxo metabolite dramatically suppressed BRAC1 expression. Thus, we have shown for the first time that the various biological activities produced by the hormone 1α,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1α,25(OH)2D3 and its natural 24-oxo metabolites. J. Cell. Biochem. 66:413-425, 1997. © 1997 Wiley-Liss, Inc.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
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