Induction of differentiation of myelogenous leukemia cells by humulone, a bitter in the hop.
The active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (VD3), inhibits proliferation and induces differentiation of myelomonocytic leukemia 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 humulone, a bitter in the hop extract for beer brewing, effectively inhibits bone resorption. In this study we examined the effect of humulone on the differentiation of human myelogenous leukemia cells. Humulone alone inhibited the growth of monoblastic leukemia U937 cells while only slightly increasing differentiation markers such as nitroblue tetrazolium (NBT)-reducing and lysozyme activities. Humulone effectively enhanced the differentiation-inducing action of VD3. Other myelomonocytic leukemia cells were induced to differentiate by VD3 and this was also enhanced by humulone. Since humulone is a less-toxic inhibitor of bone resorption, the combination of humulone and VD3 may be useful in differentiation therapy of myelomonocytic leukemia.
Honma
Y
Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Japan. honma@saitama-cc.go.jp
Tobe
H
H
Makishima
M
M
Yokoyama
A
A
Okabe-Kado
J
J
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D053138:Cyclohexenes; D004357:Drug Synergism; D002523:Edible Grain / Q000737:chemistry; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D010936:Plant Extracts / Q000737:chemistry; D013729:Terpenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000890:Anti-Infective Agents; D053138:Cyclohexenes; D010936:Plant Extracts; D013729:Terpenes; D002117:Calcitriol; C007966:humulon