Kanatani Y, Makishima M, Asahi K, Sakurai A, Takahashi N, Motoyoshi K, Nagata N, Honma Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Ina, Japan.
Biochim Biophys Acta. 1997 Oct 30;1359(1):71-9. doi: 10.1016/s0167-4889(97)00099-2.
Differanisole A, 3,5-dichloro-2-hydroxy-4-methoxy-6-n-propylbenzoic acid, inhibited growth of human myeloid leukemia cells. The compound induced G1 arrest and granulocytic differentiation of HL-60 cells, although the differentiation-inducing effect was modest. Differanisole A and 9-cis retinoic acid (9cisRA) synergistically inhibited the growth and induced functional and morphologic differentiation of HL-60 and NB4 cells, whereas the combined treatment with differanisole A and all-trans retinoic acid or 1alpha,25-dihydroxyvitamin D3 was less effective. Similar results were obtained in primary culture of leukemia cells from a patient with acute promyelocytic leukemia. The synergistic effect on growth inhibition and induction of differentiation required simultaneous treatment with differanisole A and 9cisRA. Differanisole A and an RXR-specific ligand (Ro47-5944) cooperatively inhibited the cell growth, while the combined effect of differanisole A and an RAR-specific ligand Am80 was just additive. Differanisole A in combination with 9cisRA may have implications for therapy of acute promyelocytic leukemia patients.
异茴香醚A，即3,5-二氯-2-羟基-4-甲氧基-6-正丙基苯甲酸，可抑制人髓系白血病细胞的生长。该化合物可诱导HL-60细胞的G1期阻滞和粒细胞分化，尽管其诱导分化的作用较为适度。异茴香醚A与9-顺式视黄酸（9cisRA）协同抑制HL-60和NB4细胞的生长，并诱导其功能和形态分化，而异茴香醚A与全反式视黄酸或1α,25-二羟基维生素D3联合治疗的效果较差。在一名急性早幼粒细胞白血病患者的白血病细胞原代培养中也得到了类似的结果。对生长抑制和分化诱导的协同作用需要异茴香醚A和9cisRA同时治疗。异茴香醚A与一种RXR特异性配体（Ro47-5944）协同抑制细胞生长，而异茴香醚A与一种RAR特异性配体Am80的联合作用只是相加。异茴香醚A与9cisRA联合使用可能对急性早幼粒细胞白血病患者的治疗具有重要意义。
