Lou Yin-Jun, Qian Wen-Bin, Jin Jie
Department of Hematology, Institute of Hematology, The First Affiliated Hospital, ZheJiang University College of Medicine, Hangzhou, ZheJiang, China.
Leuk Lymphoma. 2007 Jul;48(7):1400-6. doi: 10.1080/10428190701411466.
Homoharringtonine (HHT) is a plant alkaloid with antileukemic activity which is currently being used for treatment of acute and chronic leukemias. The present studies have evaluated the effect of HHT on proliferation and apoptosis in human myeloma cells. Myeloma cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic cells and cell cycle were evaluated by flow cytometry. Level of caspase-8, caspase-9, caspase-3, and DNA repair enzyme poly (ADP-ribose) polymerase (PARP), were investigated using Western blot analysis. We found that HHT significantly inhibited the proliferation of human multiple myeloma (MM) cell lines and tumor cells from patients with relapsed refractory MM in a dose-dependent manner. HHT also induced apoptosis in myeloma cells as evidenced by flow cytometric detection of annexin V binding assay. This apoptotic process was associated with the activation of caspase-8, caspase-9, caspase-3 and PARP. The results also demonstrate that HHT potentiates dexamethasone-induced killing of MM cells. These findings indicate that HHT may be effective in the treatment of MM.
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和慢性白血病。本研究评估了HHT对人骨髓瘤细胞增殖和凋亡的影响。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）法检测骨髓瘤细胞活力。通过流式细胞术评估凋亡细胞和细胞周期。使用蛋白质免疫印迹分析研究半胱天冬酶-8、半胱天冬酶-9、半胱天冬酶-3和DNA修复酶聚（ADP-核糖）聚合酶（PARP）的水平。我们发现，HHT以剂量依赖的方式显著抑制人多发性骨髓瘤（MM）细胞系以及复发难治性MM患者的肿瘤细胞的增殖。流式细胞术检测膜联蛋白V结合试验证明，HHT还可诱导骨髓瘤细胞凋亡。这种凋亡过程与半胱天冬酶-8、半胱天冬酶-9、半胱天冬酶-3和PARP的激活有关。结果还表明，HHT可增强地塞米松诱导的对MM细胞的杀伤作用。这些发现表明，HHT可能对MM治疗有效。
