施波, 韩锐. 异三尖杉酯碱诱导HL-60细胞凋亡J. 药学学报, 1998, 33(6): 407-412.
引用本文: 施波, 韩锐. 异三尖杉酯碱诱导HL-60细胞凋亡J. 药学学报, 1998, 33(6): 407-412.
Shi Bo, Han Rui. ISOHARRINGTONINE INDUCES APOPTOSIS IN HUMAN LEUKEMIA HL-60 CELLJ. Acta Pharmaceutica Sinica, 1998, 33(6): 407-412.
Citation: Shi Bo, Han Rui. ISOHARRINGTONINE INDUCES APOPTOSIS IN HUMAN LEUKEMIA HL-60 CELLJ. Acta Pharmaceutica Sinica, 1998, 33(6): 407-412.

异三尖杉酯碱诱导HL-60细胞凋亡

ISOHARRINGTONINE INDUCES APOPTOSIS IN HUMAN LEUKEMIA HL-60 CELL

  • 摘要: 用透射电镜观察、DNA凝胶电泳及流式细胞术研究了异三尖杉酯碱(IHT)诱导HL-60细胞凋亡的作用。结果证明异三尖杉酯碱能快速、显著地诱导HL-60细胞发生凋亡,其作用呈明显的浓度-效应关系和时间依赖性。IHT处理的细胞出现凋亡相关的特征性变化。在电镜观测中发现细胞核内染色质浓缩边集、核碎裂及凋亡小体形成;琼脂糖凝胶电泳可见明显的DNA梯;流式细胞光度术出现显著的G1亚峰。经10-7mol·L-1IHT处理120min,可使43.8%HL-60细胞发生凋亡。IHT有明显诱导HL-60细胞凋亡的作用,并与其细胞杀伤活性相平行,提示IHT的抗癌活性与诱导肿瘤细胞凋亡相关。这些实验结果对进一步研究、开发IHT有重要实用价值。

     

    Abstract: Harringtonine(HT), homoharringtonine(HHT) and isoharringtonine(IHT) are cephalotaxine alkaloids with anticancer activities which were isolated from Cephalotaxus hainanensis indigenous to China. Since the 1970s, HT and HHT have been developed as effective anticancer drugs in China and have been used widely in the treatment of acute nonlymphoid leukemia and chronic granulocyte leukemia. Although IHT has the advantage of low toxicity, it has not been developed as an anticancer drug because of its very low content in the plant.The cell apoptosis induced by isoharringtonine was investigated in human acute promyelocytic leukemia HL-60 cells by agarose gel electrophoresis of DNA, flow cytometry and transmission electron microscopy. In these experiments IHT showed significant and rapid apoptotic inductive effect on HL-60 cells in both concentration- and timedependent fashion. The characteristic apoptosisrelated features could be seen in IHT treated HL-60 cells. Transmission electron microscopy of IHT treated HL-60 cells displayed chromatin condensation and aggregation under the nuclear membrane, nuclear fragmentation and apoptosis body formation. Typical DNA ladder in agarose gel electrophoresis and pre-G1 peak in flow cytometric analysis were also observed in the cells exposed to IHT. The apoptotic rate could reach 43.8% in the HL-60 cells treated for 120 minutes with IHT 10-7 mol·L-1. The cytotoxicity of IHT paralleled with cell apoptosis indicating that the anticancer activity of IHT results from the induction of apoptosis. These results are important impetus for further research and development of IHT as an anticancer agent.

     

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