三尖杉酯碱和高三尖杉酯碱诱导人早幼粒白血病细胞的程序性死亡

INDUCTION OF APOPTOSIS BY HARRINGTONINE AND HOMOHARRINGTONINE IN HL-60 CELLS

体外实验证明２×ｌ０７ｍｏｌ·Ｌ－１三尖杉酯碱和１０７ｍｏｌ·Ｌ－１高三尖杉酯碱与ＨＬ－６０细胞作用４ｈ，可诱导该细胞产生程序性死亡。提取细胞ＤＮＡ进行琼脂糖凝胶电泳呈现典型的ＤＮＡ梯，同时出现细胞核染色体断裂、核固缩及细胞空泡样变等形态变化。并且在一定范围内具有作用时间和浓度依赖性，二者诱导ＨＬ－６０细胞程序性死亡作用的强弱与其细胞毒作用平行。

Abstract Harringtonine(HT ) and homoharringtonine(HHT ) are two alkaloids isolatedfrom the bark of the evergreen tree Cephalotaxus hainanensis Li in the 1970s.They were found to haveactivity against murine leukemia, Lewis lung carcinoma and B16 melanoma ,and used as anti-leukemia drugs clinically. Apoptosis is an active process of programmed cell suicide and now is beli-eved to be an important target for tumor chemotherapy. In this report ,the apoptosis inducing effect ofHT and HHT in HL-60 cells were observed. The experiments demonstrated that 2×10-7mol·L-1 ofHT and l0-7mol·L-1 of HHT could induce apoptosis in HL-60 cells when the cells were exposed toHT and HHT for 4 h. In agarose gel electrophoresis, DNA extracted from HL-60 cells treated withHT and HHT showed a typical internucleosomal DNA degradation,i.e., DNA ladder and parallelmorphological changes as nuclear chromosome segmentation and condensation as well as cytoplasmavacuolation.This effect of HT and HHT was shown to appear in a concentration-and time-dependentmanner.The efficacy of HT and HHT in inducing apoptosis of HL-60 cells was found to parallel withtheir cvtotoxic activitv in HL-60 cells.These results suggest that the mechanism of antitumor action ofHT and HHT is related to their apoptosis inducing activity.Key wards Harringtonine; Homoharringtonine; HL-60; Apoptosis