INDUCTION OF DIFFERENTIATION OF MYELOGENOUS LEUKEMIA-CELLS BY HUMULONE, A BITTER IN THE HOP

The active form of vitamin D, 1 alpha,25-dihydroxyvitamin D-3 (VD3), i nhibits proliferation and induces differentiation of myelomonocytic le ukemia cells, but its clinical use is limited by the adverse effect of hypercalcemia. VD3 mobilizes calcium stores from bone by inducing the dissolution of bone mineral and matrix. We have recently found that h umulone, a bitter in the hop extract for beer brewing, effectively inh ibits bone resorption. In this study we examined the effect of humulon e on the differentiation of human myelogenous leukemia cells. Humulone alone inhibited the growth of monoblastic leukemia U937 cells while o nly slightly increasing differentiation markers such as nitroblue tetr azolium (NBT)-reducing and lysozyme activities. Humulone effectively e nhanced the differentiation-inducing action of VD3. Other myelomonocyt ic leukemia cells were induced to differentiate by VD3 and this was al so enhanced by humulone. Since humulone is a less-toxic inhibitor of b one resorption, the combination of humulone and VD3 may be useful in d ifferentiation therapy of myelomonocytic leukemia. (C) 1998 Elsevier S cience Ltd. All rights reserved.