Calcitriol and Calcidiol Can Sensitize Melanoma Cells to Low-LET Proton Beam Irradiation

Proton beam irradiation promises therapeutic utility in the management of uveal melanoma. Calcitriol (1,25(OH)(2)D-3)the biologically active metabolite of vitamin D(3)and its precursor, calcidiol (25(OH)D-3), exert pleiotropic effects on melanoma cells. The aim of the study was to evaluate the effect of both calcitriol and calcidiol on melanoma cell proliferation and their response to proton beam irradiation. Three melanoma cell lines (human SKMEL-188 and hamster BHM Ma and BHM Ab), pre-treated with 1,25(OH)(2)D-3 or 25(OH)D-3 at graded concentrations (0, 10, 100 nM), were irradiated with 0-5 Gy and then cultured in vitro. Growth curves were determined by counting the cell number every 24 h up to 120 h, which was used to calculate surviving fractions. The obtained survival curves were analysed using two standard models: linear-quadratic and multi-target single hit. Calcitriol inhibited human melanoma proliferation at 10 nM, while only calcidiol inhibited proliferation of hamster lines at 10 and 100 nM doses. Treatment with either 1,25(OH)(2)D-3 or 25(OH)D-3 radio sensitized melanoma cells to low doses of proton beam radiation. The strength of the effect increased with the concentration of vitamin D-3. Our data suggest that vitamin D-3 may be an adjuvant that modifies proton beam efficiency during melanoma therapy.