Evaluation of C-2-substituted 19-nor-1α,25-dihydroxyvitamin D3 analogs as therapeutic agents for prostate cancer

Comprehensive Association Analysis of the Vitamin D Pathway Genes, VDR, CYP27B1, and CYP24A1, in Prostate Cancer

“…Consistent with this finding, a similar antiproliferative effect was described for 25(OH)D as compared with 1,25(OH) 2 D in human prostate cancer cells in primary cultures that express 1-a-hydroxylase (30)(31)(32). In prostate cancer cells, 1-a-hydroxylase activity is down-regulated whereas high levels of 24-hydroxylase are found in prostate cancer cells (31,33), suggesting lower concentration of the metabolically active form of vitamin D in malignant cells.…”

Comparative Genome Analysis Identifies the Vitamin D Receptor Gene as a Direct Target of p53-Mediated Transcriptional Activation

“…Vitamin D analogues, such as 1,25(OH) 2 D 3 , can inhibit the growth of various types of malignant cells, including breast, prostate, colon, skin, and brain cancer cells, as well as myeloid leukemia cells (12,13,15,29). Moreover, 1,25(OH) 2 D 3 shows antitumor activity in animal models (30) and, accordingly, clinical studies to evaluate the effect of vitamin D analogues in patients with colorectal cancer and other neoplasms are under way (12,13).…”

Kinetic Studies of 25-Hydroxy-19-nor-vitamin D3and 1α,25-Dihydroxy-19-nor-vitamin D3Hydroxylation by CYP27B1 and CYP24A1

“…Since the discovery of 1␣-hydroxylase in prostate cells in 1998, several groups have demonstrated that 25(OH)D 3 has the ability to inhibit cell proliferation in cultured prostate cells and concluded that 25(OH)D 3 was converted to 1␣,25(OH) 2 D 3 by prostatic CYP27B1 in an autocrine fashion before exerting antiproliferative activity (Barreto et al, 2000;Chen et al, 2000;Hsu et al, 2001). Whitlatch et al (2002) further established the role of CYP27B1 by demonstrating that LNCaP prostate cancer cells, which were not responsive to 25(OH)D 3 inhibition, became responsive after the cells were transfected with the CYP27B1 cDNA plasmid.…”