GROWTH-INHIBITION OF HUMAN-MELANOMA CELLS BY VITAMIN-D ANALOGS

The antiproliferative activity of 1,25(OH)(2)-vitamin D-3, and four vi tamin D analogs was assessed in RPMI-7951, a human melanoma cell line which expresses the vitamin D receptor. Proliferation assays consisted of a [H-3]-thymidine incorporation assay, and a 6-day growth study. T he affinity of vitamin D analogs for vitamin D receptor relative to 12 5(OH)(2)-vitamin D-3 was determined with a hydroxyapatite-based compet itive binding assay. For the proliferation assays, cells were treated with 10(-8) M 1,25(OH)(2)-vitamin D-3, 1,25(OH)(2)-16-ene-23-yne-vitam in D-3 (Ro 23-7553), 1,25(OH)(2)-16-ene-23-yne-26,27-hexafluoro-vitami n D-3 (Ro 24-5531), 1,25(OH),-16,23Z-diene-26,27-hexafluoro-vitamin D- 3 (Ro 25-5317), and 1 alpha-fluoro-25(OH)- 16-ene-23-yne-hexafluoro-vi tamin D-3 (Ro 24-5583). 1,25(OH)(2)-vitamin D-3 and the four analogs a ll significantly inhibited melanoma cell growth (P<0.05). Competitive binding of the vitamin D analogs to vitamin D receptor ranged from 51% to 72% that of 1,25(OH)(2)-vitamin D-3, suggesting a receptor-mediate d response. These results demonstrate that analogs of 1,25(OH)(2)-vita min D-3 are potent antiproliferative agents in human melanoma cells in vitro.