THE POTENT ANTIPROLIFERATIVE EFFECT OF 20-EPI ANALOGS OF 1,25-DIHYDROXYVITAMIN-D-3 IN HUMAN BREAST-CANCER MCF-7 CELLS IS RELATED TO PROMOTER SELECTIVITY

The hormone 1,25-dihydroxyvitamin D-3 (VD) has a potential use as an a nti-tumor agent, but its clinical applications are restricted by its s trong calcemic activity. This has led to the development of VD analogu es with selectively increased growth inhibitory activity. One of the m ost potent analogues is KH1060, which is a 20-epi-22-oxa-derivative of VD. In human breast cancer MCF-7 cells, we studied the growth-inhibit ory activities of a set of 8 analogues that cover conservative structu ral changes from 20-epi-VD (MC1288) to KH1060. In the same cellular sy stem, we analyzed the potential of these 8 analogues to stimulate repo rter gene activity driven by a recently discovered novel-type VD respo nse element. We found that this VD response element is more appropriat e than classical VD response elements to correlate anti-proliferative effects of VD analogues with their gene-regulatory properties. (C) 199 6 Wiley-Liss, Inc.