Effect of hexafluoro-1,25-dihydroxyvitamin D3 and sodium butyrate combination on differentiation and proliferation of HL-60 leukemia cells.

We have investigated the combined effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and its fluoroanalog 26,26,26,27,27,27-hexafluoro-1,25-(OH)2D3 [F6-1,25-(OH)2D3] with sodium butyrate (NaB) on growth and differentiation of HL-60 human promyelocytic leukemia cells. F6-1,25-(OH)2D3 was 10-fold more active than 1,25-(OH)2D3 for induction of cell differentiation in HL-60 cells. Exposure to suboptimal concentration of F6-1,25-(OH)2D3 and NaB had synergistic effects compared to that of F6-1,25-(OH)2D3 or NaB alone and in the presence of 0.1-0.3 mM NaB, the dosage of F6-1,25-(OH)2D3 required to inhibit cell growth and colony formation and to induce cell differentiation was significantly reduced. The mechanism for the synergistic effect is probably that NaB increases cytoplasm content and nuclear binding of 1,25-(OH)2D3.