The potent anti-proliferative effect of 20-EPI analogues of 1,25 dihydroxyvitamin D3 in human breast-cancer MCF-7 cells is related to promoter selectivity

✍ Scribed by Christina Mørk Hansen; Carina Danielsson; Carsten Carlberg

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 458 KB
• Volume: 67
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960904)67:5<739::aid-ijc24>3.0.co;2-z

✦ Synopsis

The hormone I ,25-dihydroxyvitamin D3 (VD) has a potential use as an anti-tumor agent, but its clinical applications are restricted by its strong calcemic activity. This has led to the development of VD analogues with selectively increased growthinhibitory activity. One of the most potent analogues is KH 1060, which is a 20-epi-22-oxa-derivative of VD. In human breast cancer MCF-7 cells, we studied the growth-inhibitory activities of a set of 8 analogues that cover conservative structural changes from 20-epi-VD (MC1288) to KH1060. In the same cellular system, we analyzed the potential of these 8 analogues to stimulate reporter gene activity driven by a recently discovered novel-type VD response element. We found that this VD response element is more appropriate than classical VD response elements to correlate anti-proliferative effects of VD a'nalogues with their gene-regulatory properties.