24- and 26-homo-1,25-dihydroxyvitamin D3: preferential activity in inducing differentiation of human leukemia cells HL-60 in vitro.

1,25-Dihydroxyvitamin D3, the hormonal form of vitamin D3, promotes the differentiation of HL-60 human promyelocytic leukemia cells into monocytes. Differentiation changes include the induction of phagocytosis, the initiation of nitroblue tetrazolium-reducing activity, and the appearance of nonspecific acid esterase. We have found that the 24-homo- and 26-homo-1,25-dihydroxyvitamin D3 and their delta 22 analogues are 10-fold more potent than 1,25-dihydroxyvitamin D3 in inducing differentiation of HL-60 cells in vitro. In vivo, these analogues show activity similar to 1,25-dihydroxyvitamin D3 in stimulating intestinal calcium transport in vitamin D-deficient rats. The 24-homoanalogues are significantly less active, whereas the 26-homo derivatives are more active than the natural hormone in mobilizing calcium from bone. This unusual activity pattern cannot be explained on the basis of the affinity of these analogues for the 1,25-dihydroxyvitamin D3 intracellular receptor: both 24-homo- and 26-homo-1,25-dihydroxyvitamin D3 have the same effectiveness as 1,25-dihydroxyvitamin D3 in displacing the tritiated hormone from its receptor in rat intestine or HL-60 cells. These analogues of 1,25-dihydroxyvitamin D3 may be of some interest as possible therapeutic substances, or as tools in understanding the action of 1,25-dihydroxyvitamin D3 in inducing differentiation.