Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs
Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs
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DOI：
10.1016/s0145-2126(97)00061-1
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发表时间：
1997-09-01
影响因子：
2.7
通讯作者：
Nakaya, K
中科院分区：
文献类型：
--
作者：
Hashimoto, S;Jing, YK;Nakaya, K
用10（-7）M蟾蜍灵处理人白血病HL-60细胞后，拓扑异构酶（topo）Ⅱ α和Ⅱ β的含量及topo Ⅱ的活性均明显下降，18小时后几乎检测不到。topo II mRNA的水平开始下降后立即开始与蟾毒灵治疗，与随后的topo II α蛋白的量减少。这些变化先于DNA片段化，这是凋亡的典型特征。结果表明，蟾蜍灵引起拓扑异构酶II α mRNA的稳态水平显着下降，从而导致酶的量和活性的降低，并诱导细胞凋亡。蟾蜍灵降低拓扑异构酶II α的水平，也观察到在其他线的人白血病细胞，如ML 1和U937。结果表明：10（-7）M蟾蜍灵预处理HL-60细胞6 h，可增强顺铂和维甲酸对HL-60细胞生长的抑制作用，并增强对细胞死亡的诱导作用。(C)1997 Elsevier Science Ltd.
When human leukemia HL-60 cells were treated with 10(-7) M bufalin, the amounts of both topoisomerase (topo) II alpha and II beta and the activity of topo II decreased markedly and were almost undetectable 18h after the start of treatment. The level of topo II mRNA started to decrease immediately after the start of treatment with bufalin, with a subsequent decrease in the amount of topo II alpha protein. These changes preceded the fragmentation of DNA, a typical feature of apoptosis. The results suggest that bufalin caused a marked decrease in the steady-state level of topo II alpha mRNA, which led to a decrease in the amount and activity of the enzyme and to the induction of apoptosis. A reduction in the level of topo II alpha by bufalin was also observed in other lines of human leukemia cells such as ML1 and U937. The results were exploited to potentiate the effects of cisplatin and retinoic acid (RA) on HL-60 cells: pretreatment of HL-60 cells with 10(-7) M bufalin for 6 h increased the inhibitory effects of cisplatin and RA on cell growth and enhanced the induction of cell death. (C) 1997 Elsevier Science Ltd.