Lishner M, Shur I, Bleiberg I, Rudi A, Kashman Y, Fabian I
Hematology Unit, Meir Hospital, Kfar Saba, Israel.
Leukemia. 1995 Sep;9(9):1543-8.
Results of chemotherapy in acute myeloid leukemia (AML) have improved slowly or not at all in the last decade. We evaluated the effect of Eilatin and Norsegoline, two new aromatic alkaloids derived from the Red Sea purple tunicate Eudistoma sp., on in vitro proliferation and differentiation of leukemic cell lines and blast cells of three AML patients. These biological properties were studied in two complementary culture methods. The first is a clonogenic assay that supports colony formation in agar and reflects terminal divisions. The second is a suspension assay where clonogenic cells increase exponentially and reflects self-renewal. Eilatin and Norsegoline, at micromolar concentrations, suppressed, in a dose-dependent manner, both primary colony formation in agar and the recovery of clonogenic cells from suspension culture in the investigated cell lines and in fresh blasts. Furthermore, both alkaloids were more effective in inhibiting clonogenic cells grown in suspension than primary colonies grown in agar. In addition, these agents were able to induce immunophenotypic maturation of leukemic cell lines (upregulation of CD14 and CD11 and down-regulation of CD34 antigens). Our results indicate that Eilatin and Norsegoline significantly inhibit self-renewal capacity of leukemic progenitors and may provide a useful new tool for the treatment of AML patients.
在过去十年中，急性髓系白血病（AML）的化疗效果改善缓慢甚至毫无进展。我们评估了两种源自红海紫色被囊动物Eudistoma sp.的新型芳香生物碱——艾拉汀和诺塞戈林，对白血病细胞系以及三名AML患者原始细胞的体外增殖和分化的影响。这些生物学特性通过两种互补的培养方法进行研究。第一种是克隆形成试验，它支持细胞在琼脂中形成集落并反映终末分裂。第二种是悬浮试验，其中克隆形成细胞呈指数增长并反映自我更新能力。在微摩尔浓度下，艾拉汀和诺塞戈林以剂量依赖的方式抑制了所研究细胞系和新鲜原始细胞在琼脂中的初级集落形成以及从悬浮培养中回收克隆形成细胞。此外，这两种生物碱对抑制悬浮培养的克隆形成细胞比抑制琼脂中生长的初级集落更有效。另外，这些药物能够诱导白血病细胞系的免疫表型成熟（CD14和CD11上调以及CD34抗原下调）。我们的结果表明，艾拉汀和诺塞戈林显著抑制白血病祖细胞的自我更新能力，可能为AML患者的治疗提供一种有用的新工具。
