SYNTHETIC ANALOGS OF VITAMIN-D-3 HAVE INHIBITORY EFFECTS ON BREAST-CANCER CELL-LINES

Background: 1,25-dihydroxycholecalciferol has been previously reported to negatively regulate human bi east cancer cell growth. Material and methods: The antiproliferative effect of 1,25-dihydroxycholecalcifero l (Ro 21-5535) and of the two non hypercalcemic analogs oxy-16-ene-23- yne-26,27-hexafluorocholecalciferol, Ro 24-5531 and ne-23-yne-26,27-he xafluoro-19-nor-cholecalciferol, Ro 25-6760) was studied in MCF-7 and MDAMB-468 human breast cancer cell lines. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Steroid receptor modulatio n was investigated by radioligand assay. Results: The most effective d rug was the Ro 25-6760 which at concentrations ranging between 1-100 n M caused a dose dependent growth inhibition apparently due to accumula tion in G(0)/G(1). Vitamin D3 analogs (10 nM) significantly counteract ed the growth stimulation induced by TGF-a and IGF-I as well as the pa racrine stimulation observed in co-cultures. They antagonized estradio l-promoted growth stimulation and progestrone receptor induction in MC F-7 cells. Conclusion: Vitamin D3 analogs represent a class of clinica lly attractive drugs for treatment of breast cancer due to their abili ty to counter act estradiol and growth factor induced growth stimulati on.