Previous studies have suggested that 1,25(OH)(2)D-3, the active form of vitamin D-3, may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D-3 has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH)(2)D-3 induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in this model. Moreover, 1,25(OH)(2)D-3 failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D-3. (c) 2005 Elsevier Inc. All rights reserved.