Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP)
Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP)
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DOI：
10.1002/ajh.20100
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发表时间：
2004-07-01
影响因子：
12.8
通讯作者：
Tong, XM
中科院分区：
文献类型：
--
作者：
Lou, YJ;Jie, J;Tong, XM
高三尖杉酯碱(HHT)是一种具有抗白血病活性的植物生物碱，目前正被用于治疗急性、慢性白血病和MDS。在这项研究中，我们发现HHT可以诱导多种人髓系白血病细胞系(U937、HL-60、HEL、THP和K562)的凋亡。在HHT作用下，U937和HL60细胞发生迅速的凋亡，表现为膜联蛋白V结合能力的增加，caspase-3的激活，以及聚(ADP-核糖)聚合酶(PARP)的裂解。此外，在HHT诱导的细胞死亡过程中，bax的表达上调，而bcl2的表达仅略有下降。重要的是，对来自急性髓系白血病患者的原代白血病细胞的治疗导致了快速的细胞凋亡。因此，我们的数据提供了HHT的机制，并证明了HHT在人类髓系白血病治疗中的应用。(C)2004年Wiley-Liss公司
Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia. (C) 2004 Wiley-Liss, Inc.