Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.
Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.
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ICariside II在U937急性髓样白血病细胞中诱导凋亡：与STAT3相关信号失活的作用。
DOI：
10.1371/journal.pone.0028706
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kim SH
中科院分区：
文献类型：
--
作者：
Kang SH;Jeong SJ;Kim SH;Kim JH;Jung JH;Koh W;Kim JH;Kim DK;Chen CY;Kim SH
本研究的目的是研究从朝鲜淫羊藿根中分离纯化的淫羊藿苷II对人急性髓系白血病(AML)细胞株U937的抑制作用。淫羊藿苷II以剂量和时间依赖的方式抑制U937细胞的生长。在这一抗增殖过程中，该中药复方使细胞对凋亡敏感，表现为促进亚G1期细胞群的聚集，并增加末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)阳性细胞。淫羊藿苷II能够激活caspase-3，并以时间依赖的方式切割聚(ADP-核糖)聚合酶(PARP)。同时，淫羊藿苷II可下调U937细胞中抗凋亡蛋白bclxl和Survivin的表达。此外，淫羊藿苷II还能抑制STAT3的磷酸化和功能，进而抑制STAT3上游激活剂Janus激活蛋白2(JAK2)的激活，并呈剂量和时间依赖关系。淫羊藿苷II还能促进蛋白酪氨酸磷酸酶(PTP)SH2结构域磷酸酶(SHP)-1的表达，而过钒酸钠(PTP抑制剂)可阻止淫羊藿苷II诱导的U937细胞凋亡和STAT3失活。此外，用SHP-1特异性siRNA沉默SHP-1可显著阻断淫羊藿苷II诱导的U937细胞中STAT3的失活和凋亡。我们的结果表明，淫羊藿苷II通过靶向STAT3相关信号，使U937细胞对凋亡敏感，可能是一种有效的急性髓系白血病化疗药物。
The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937. Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-xL and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells. Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.
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通讯作者：
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