Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells.
Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells.
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发表时间：
1993
期刊：
影响因子：
11.4
通讯作者：
K. Bhalla;A. M. Ibrado;E. Tourkina;Caroline Tang;M. Mahoney;Yue Huang
中科院分区：
文献类型：
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作者：
K. Bhalla;A. M. Ibrado;E. Tourkina;Caroline Tang;M. Mahoney;Yue Huang
目前的研究结果表明，暴露于临床可达到的紫杉醇浓度的人髓性白血病HL-60和KG-1细胞产生约200个碱基对倍数的核小体间DNA片段，和细胞发生程序性细胞死亡（PCD）或凋亡的形态学变化的特征。紫杉醇诱导的PCD与HL-60细胞悬浮培养生长和克隆形成存活的显着抑制有关。此外，紫杉醇治疗降低了BCL-2癌基因的表达，这是已知的阻断PCD。暴露于紫杉醇适度降低了c-myc的表达，但没有诱导c-jun的表达-这已经注意到了各种DNA相互作用，抗白血病药物。这些结果表明，紫杉醇诱导白血病细胞死亡可能部分通过选择性的，但基因导向的和主动的PCD机制。
The present results demonstrate that the exposure of human myeloid leukemia HL-60 and KG-1 cells to clinically achievable concentrations of taxol produced internucleosomal DNA fragmentation of approximately 200 base-pair multiples, and the morphologic changes characteristic of cells undergoing programmed cell death (PCD) or apoptosis. Taxol-induced PCD was associated with a marked inhibition of suspension culture growth and clonogenic survival of HL-60 cells. In addition, taxol treatment decreased BCL-2 oncogene expression, which is known to block PCD. The exposure to taxol moderately decreased c-myc expression, but did not induce c-jun expression--which has been previously noted for a variety of DNA interactive, antileukemic drugs. These findings indicate that taxol may induce leukemic cell death partly by the alternative but gene-directed and active mechanism of PCD.