SELECTIVE INHIBITORY EFFECT OF BUFALIN ON GROWTH OF HUMAN TUMOR-CELLS IN-VITRO - ASSOCIATION WITH THE INDUCTION OF APOPTOSIS IN LEUKEMIA HL-60 CELLS
SELECTIVE INHIBITORY EFFECT OF BUFALIN ON GROWTH OF HUMAN TUMOR-CELLS IN-VITRO - ASSOCIATION WITH THE INDUCTION OF APOPTOSIS IN LEUKEMIA HL-60 CELLS
复制标题
DOI：
10.1111/j.1349-7006.1994.tb02408.x
复制
发表时间：
1994-06-01
期刊：
影响因子：
--
通讯作者：
NAKAYA, K
中科院分区：
文献类型：
--
作者：
JING, YK;OHIZUMI, H;NAKAYA, K
我们发现中药蟾酥的活性成分蟾酥对多种人类癌细胞的生长具有选择性抑制作用。为了研究蟾酥对人癌细胞的生长抑制作用是否与细胞凋亡有关，我们用蟾酥对人白血病细胞进行处理。HL-6D、ML1和U937白血病细胞在10(-8)M及以上剂量下均可见核固缩和碎裂。流式细胞仪分析显示，经蟾酥处理的这些细胞的DNA片段化小于G1期。琼脂糖凝胶电泳法分析，蟾酥处理的HL-60细胞DNA呈梯状条带。随着蟾酥灵浓度的增加，HL-60细胞DNA合成和拓扑异构酶II活性受到明显抑制。诱导HL-60细胞凋亡所需浓度为10(-8)M，与喜树碱相当，但低于顺铂、VP16和全反式维甲酸等抗癌药物。用10(-6)M的蟾酥作用于人单核细胞和多形核细胞24 h后，未观察到细胞发生凋亡的现象，提示蟾酥的生长抑制作用与诱导HL-60细胞的凋亡有关，并提示其在肿瘤诱导分化治疗中的作用。
We found that bufalin, an active principle of the Chinese medicine chan'su, has selective inhibitory effects on the growth of various human cancer cells. In order to examine whether the growth-inhibitory effect of bufalin on human cancer cells is associated with apoptosis, human leukemia cells were treated with bufalin. HL-6D, ML1, and U937 leukemia cells treated with bufalin at 10(-8) M and above had condensed and fragmented nuclei. Flow cytometric analysis of these cells treated with bufalin showed fragmented DNA smaller than that of the G1 phase. DNA of HL-60 cells treated with bufalin showed a ladder pattern characteristic of apoptosis, as analyzed by agarose gel electrophoretic analysis. DNA synthesis and topoisomerase II activity of HL-60 cells were markedly inhibited as the concentration of bufalin was increased. The concentration needed for inducing apoptosis of HL-60 cells was 10(-8) M, which is comparable to that of camptothecin, but lower than those of other antitumor drugs such as cisplatin, VP16 and all-trans retinoic acid. Apoptosis was not observed when human mononuclear and polymorphonuclear cells were treated with 10(-6) M bufalin for 24 h. These results indicate the association of the growth-inhibitory effect of bufalin with the induction of apoptosis, at least in HL-60 cells, and suggest the usefulness of bufalin for differentiation-apoptosis-inducing therapy for cancer.