Long-Term Exposure of HL60 Cells to 1,25-Dihydroxyvitamin D 3 Reduces Their Tumorigenicity: A Model for Cancer Chemoprevention

Abstract

Abstract

Several lines of evidence suggest that 1,25-dihydroxyvitamin D₃ (1,25D₃) may be important in chemoprevention of human cancer. Here, we show that human promyelocytic leukemia cells HL60 cultured in the presence of 30 nM 1,25D₃ (30A cells) for 3 years exhibited a reduced rate of tumor growth when injected into nu/nu mice, while cells grown in 40 nM 1,25D₃ (40AF cells) failed to form detectable tumors in 11 out of the 12 inoculated mice. Interestingly, both 30A and 40AF cells grew approximately twice as fast as the parental HL60-G cells under tissue culture conditions, even in the presence of 1,25D₃, to which they developed resistance. Tests of the susceptibility of these cells to natural killer (NK) cell cytotoxicity showed that 40AF, but not HL60-G or 30A cells, were targets for the murine spleen NK cells. However, lysis of 30A cells was also detected when human NK cells were used in this assay, though the effector-to-target cell ratio necessary to obtain significant lysis above background levels was higher for 30A (80:1) than for 40AF (10:1) cells. These results suggest a mechanism for the reported chemopreventive effects of sunlight-generated 1,25D₃ or dietary vitamin D₃.