Honma Y, Tobe H, Makishima M, Yokoyama A, Okabe-Kado J
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Japan.
Leuk Res. 1998 Jul;22(7):605-10. doi: 10.1016/s0145-2126(98)00046-0.
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.
维生素D的活性形式，1α，25 - 二羟基维生素D3（VD3），可抑制骨髓单核细胞白血病细胞的增殖并诱导其分化，但其临床应用因高钙血症的不良反应而受到限制。VD3通过诱导骨矿物质和基质的溶解来动员骨中的钙储备。我们最近发现，啤酒花提取物中一种用于啤酒酿造的苦味成分——葎草酮，能有效抑制骨吸收。在本研究中，我们检测了葎草酮对人骨髓性白血病细胞分化的影响。单独使用葎草酮可抑制单核细胞白血病U937细胞的生长，同时仅轻微增加分化标志物，如硝基蓝四氮唑（NBT）还原活性和溶菌酶活性。葎草酮有效增强了VD3的诱导分化作用。其他骨髓单核细胞白血病细胞可被VD3诱导分化，且这种诱导作用也因葎草酮而增强。由于葎草酮是一种毒性较小的骨吸收抑制剂，葎草酮与VD3联合使用可能对骨髓单核细胞白血病的分化治疗有用。
