VITAMIN-D DERIVATIVES IN COMBINATION WITH 9-CIS RETINOIC ACID PROMOTEACTIVE CELL-DEATH IN BREAST-CANCER CELLS

The effects of the novel vitamin D analogue, EB1089 alone, or in combi nation with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and inc reasing p53 protein levels in MCF-7 cell cultures following 96h treatm ent. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and upregulation of bcl-2 and p53 respectively. Furthe rmore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The obse rvation that EB1089 and 9-cis RA act in a cooperative manner to enhanc e induction of apoptosis in these cells may have therapeutic implicati ons.