Compounds > 1-25-dihydroxy-24-oxo-vitamin-d3

1-25-dihydroxy-24-oxo-vitamin-d3 and Breast-Neoplasms

1-25-dihydroxy-24-oxo-vitamin-d3 has been researched along with Breast-Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for 1-25-dihydroxy-24-oxo-vitamin-d3 and Breast-Neoplasms

Article	Year
Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects. Journal of cellular biochemistry, 1997, Sep-01, Volume: 66, Issue:3 The seco-steroid hormone, 1 alpha, 25 dihydroxyvitamin D3 (1 alpha,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 1 alpha,25(OH)2D3 and two of its potent synthetic analogs (1 alpha,25-(OH)2-16-ene-D3 and 1 alpha,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1 alpha,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 1 alpha,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 1 alpha,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1 alpha,25(OH)2D3 and its natural 24-oxo metabolites. Topics: Apoptosis; bcl-2-Associated X Protein; BRCA1 Protein; Breast Neoplasms; Cadherins; Calcitriol; Cell Cycle; Cell Cycle Proteins; Cell Division; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins; HL-60 Cells; Humans; Male; Microtubule-Associated Proteins; Neoplasms; Prostatic Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Tumor Suppressor Proteins	1997

Article

Year

Vitamin D3 analogs and their 24-oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects.

Journal of cellular biochemistry, 1997, Sep-01, Volume: 66, Issue:3

The seco-steroid hormone, 1 alpha, 25 dihydroxyvitamin D3 (1 alpha,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 1 alpha,25(OH)2D3 and two of its potent synthetic analogs (1 alpha,25-(OH)2-16-ene-D3 and 1 alpha,25-(OH)2-20-epi-D3) using a rat kidney perfusion system. We have found that the 24-oxo metabolites of both 1 alpha,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 1 alpha,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 1 alpha,25(OH)2D3 and some of its analogs may represent a combination of actions by the hormone 1 alpha,25(OH)2D3 and its natural 24-oxo metabolites.

Topics: Apoptosis; bcl-2-Associated X Protein; BRCA1 Protein; Breast Neoplasms; Cadherins; Calcitriol; Cell Cycle; Cell Cycle Proteins; Cell Division; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Cyclins; HL-60 Cells; Humans; Male; Microtubule-Associated Proteins; Neoplasms; Prostatic Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Tumor Suppressor Proteins

1997