Suh N, Luyengi L, Fong H H, Kinghorn A D, Pezzuto J M
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
Anticancer Res. 1995 Mar-Apr;15(2):233-9.
Terminal differentiation of human promyelocytic leukemia (HL-60) cells can be induced by a variety of chemical agents and this process can be monitored readily by the generation of morphologically, histochemically, and functionally mature granulocytes and monocytes/macrophages. The availability of this model has heightened interest in the possible therapeutic role of inducers of myeloid differentiation for the treatment of leukemia and other neoplasms. In addition, however, potent cancer chemopreventive agents induce HL-60 cell differentiation at very low dose levels. Thus, as part of our search for natural product chemopreventive agents, extracts derived from nearly 400 plants were tested for their potential to induce HL-60 cell differentiation. As a result, 17 plant extracts were judged to be active (ED50 values < or = 4 micrograms/ml). One of most potent leads was an extract derived from Dirca occidentalis Gray (Thymelaeaceae) (ED50, 0.14 micrograms/ml), and bioassay-guided fractionation led to the identification of genkwanin (I), (+/-)-lariciresinol (II) and sitoindoside II (IV) as active principles, with ED50 values of 18.3, 1.1 and 0.069 microM, respectively. Based on these data, we conclude that the HL-60 cell differentiation system is a valid and useful model for the discovery of natural product cancer chemopreventive or chemotherapeutic agents.
人早幼粒细胞白血病（HL-60）细胞的终末分化可由多种化学试剂诱导，并且这一过程可通过形态学、组织化学和功能上成熟的粒细胞及单核细胞/巨噬细胞的生成来轻松监测。该模型的可用性提高了人们对髓系分化诱导剂在白血病和其他肿瘤治疗中可能的治疗作用的兴趣。然而，此外，强效癌症化学预防剂在非常低的剂量水平就能诱导HL-60细胞分化。因此，作为我们寻找天然产物化学预防剂工作的一部分，对近400种植物的提取物进行了诱导HL-60细胞分化潜力的测试。结果，17种植物提取物被判定具有活性（半数有效剂量值≤4微克/毫升）。最有效的先导物之一是西方毛瑞香（瑞香科）提取物（半数有效剂量，0.14微克/毫升），生物测定导向的分级分离鉴定出芫花素（I）、（±）-落叶松脂醇（II）和水飞蓟宾糖苷II（IV）为活性成分，其半数有效剂量值分别为18.3、1.1和0.069微摩尔。基于这些数据，我们得出结论，HL-60细胞分化系统是发现天然产物癌症化学预防剂或化学治疗剂的有效且有用的模型。
