Induction of differentiation of human promyelocytic leukemia (HL-60) cells by teleocidin and phorbol-12-myristate-13-acetate.
Induction of differentiation of human promyelocytic leukemia (HL-60) cells by teleocidin and phorbol-12-myristate-13-acetate.
复制标题
teleocidin 和 phorbol-12-myristate-13-acetate 诱导人早幼粒细胞白血病 (HL-60) 细胞分化。
作者：
E. Huberman;G. Braslawsky;M. Callaham;H. Fugiki
人早幼粒细胞白血病细胞（HL-60）在肿瘤促进剂佛波酯（phorbol-12-myristate-13-acetate）和非佛波酯（teleocidin）的促进下以剂量依赖的方式被诱导分化为巨噬细胞样细胞。对佛波醇-12-肉豆蔻酸酯-13-乙酸酯的分化诱导具有抗性的HL-60细胞变体，命名为R-59，也对teleocidin的分化诱导具有抗性。分化是由形态成熟细胞的百分比和溶菌酶和非特异性酯酶活性的增加来确定的。这两种化合物通过阻断HL-60细胞进入细胞周期的合成期来抑制HL-60细胞的生长，48 h后细胞聚集在G1期。在R-59细胞中未观察到这种效应。然而，他们是敏感的父母HL-60细胞，诱导剂不被认为是肿瘤促进剂，如二甲基亚砜和视黄酸。然而，这些诱导剂导致HL-60和R-59细胞分化为粒细胞样细胞。这些结果表明，Teleocidin在HL-60和R-59细胞中产生的作用与佛波醇-12-肉豆蔻酸酯-13-乙酸酯引起的作用相似。在这两种细胞类型中产生这种效果的药物可能代表潜在的肿瘤促进剂进行了讨论。
Human promyelocytic leukemia cells (HL-60) were induced to differentiate into macrophage-like cells in a dose-dependent manner by the tumor promoters phorbol-12-myristate-13-acetate and teleocidin, a non-phorbol ester promoter. An HL-60 cell variant, designated as R-59, which is resistant to differentiation induction by phorbol-12-myristate-13-acetate was also resistant to differentiation induction by teleocidin. Differentiation was determined by increases in the percent of morphologically mature cells and in lysozyme and nonspecific esterase activities. Both compounds inhibited the growth of HL-60 cells by blocking them from entering the synthesis phase of the cell cycle with an accumulation of cells after 48 h in G1 phase. No such effects were observed in the R-59 cells. They were, however, as susceptible as the parent HL-60 cells, to inducers which are not considered to be tumor promoters such as dimethylsulfoxide and retinoic acid. However, these inducers cause the HL-60 and R-59 cells to differentiate into granulocyte-like cells. These results indicate that teleocidin produces in both the HL-60 and R-59 cells effects which are similar to those cause by phorbol-12-myristate-13-acetate. The possibility that agents producing such effects in these two cell types may represent potential tumor promoters is discussed.