Yinjun Lou, Jie Jin, Weilai Xu, Xiangming Tong
Institute of Hematology, First Affiliated Hospital of ZheJiang University, Hangzhou, China.
Am J Hematol. 2004 Jul;76(3):199-204. doi: 10.1002/ajh.20100.
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.
高三尖杉酯碱（HHT）是一种具有抗白血病活性的植物生物碱，目前正用于治疗急性、慢性白血病和骨髓增生异常综合征（MDS）。在本研究中，我们表明HHT可诱导多种人髓系白血病细胞系（U937、HL-60、HEL、THP和K562）发生凋亡。U937和HL60细胞在用HHT处理后迅速发生凋亡，这表现为膜联蛋白V结合能力增强、半胱天冬酶-3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bcl-2的表达仅略有下降。重要的是，对从急性髓系白血病患者获得的原代白血病细胞进行处理后，细胞迅速发生凋亡。因此，我们的数据揭示了HHT的作用机制，并证明了HHT在治疗人髓系白血病中的应用合理性。
