Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways
Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways
复制标题
淫羊藿素通过 MAPK/ERK 和 PI3K/AKT 信号通路诱导 AML 细胞凋亡
DOI：
10.1007/s12185-013-1317-9
复制
发表时间：
2013-05-01
影响因子：
2.1
通讯作者：
Wang, Jianxiang
中科院分区：
文献类型：
--
作者：
Li, Qihui;Huai, Lei;Wang, Jianxiang
淫羊藿苷是淫羊藿苷的水解产物，是从传统中草药淫羊藿中分离得到的。淫羊藿苷抑制几种肿瘤细胞系的增殖，但其对急性髓性白血病（AML）的作用及其机制仍有待确定。在本研究中，我们证明了淫羊藿苷抑制人AML细胞系NB 4，HL 60和U937的增殖，在剂量和时间依赖性的方式。重要的是，淫羊藿苷对15名新诊断的AML患者的骨髓单个核细胞显示出抗白血病活性。流式细胞仪分析表明淫羊藿苷诱导AML细胞凋亡。淫羊藿苷诱导caspase-9、-3、-7的活化和PARP的裂解，如通过Western印迹所测量的。淫羊藿苷下调p-ERK和p-AKT，抑制c-myc的表达。这些结果表明，淫羊藿苷是一个有前途的候选药物治疗急性髓细胞白血病。淫羊藿苷抗AML活性的潜在机制与抑制MAPK/ERK和PI 3 K/AKT信号和下调c-myc有关。
Icaritin, a hydrolytic product of icaritin, is isolated from the traditional Chinese medicinal herb epimedium. Icaritin inhibits the proliferation of several tumor cell lines, but its effect on acute myeloid leukemia (AML) and underlying mechanisms remain to be identified. In the present study, we demonstrated that icaritin inhibits the proliferation of human AML cell lines NB4, HL60, and U937, in a dose- and time-dependent manner. Importantly, icaritin showed anti-leukemia activity on bone marrow mononuclear cells from 15 newly diagnosed AML patients. Flow cytometry analyses indicated that icaritin induces AML cells apoptosis. Icaritin induced activation of caspase-9, -3, -7 and the cleavage of PARP as measured by Western blotting. Icaritin downregulates p-ERK and p-AKT and inhibits the expression of c-myc. These results suggest that icaritin is a promising candidate drug for the treatment of AML. The underlying mechanisms of icaritin anti-AML activity are associated with inhibition of the MAPK/ERK and PI3K/AKT signals and downregulation of c-myc.