Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells
Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells
复制标题
DOI：
10.1182/blood-2012-11-466219
复制
发表时间：
2013-05-02
期刊：
影响因子：
20.3
通讯作者：
Guo, Qinglong
中科院分区：
文献类型：
--
作者：
Chen, Yan;Hui, Hui;Guo, Qinglong
汉黄芩苷是从黄芩中提取的主要黄酮类成分。它是一种受欢迎的中草药，具有治疗恶性血液病的潜力。在这项研究中，我们研究了汉黄芩苷在急性髓性白血病（AML）细胞系和原代患者来源的AML细胞中的抗癌作用。汉黄芩苷在体外和体内均具有抗增殖作用。此外，它通过诱导G1期阻滞和促进分化，有效地抑制了U937和HL-60细胞的增殖。我们还证明，汉黄芩苷显着增加的磷脂scramblase 1（PLSCR 1）的转录，由于其对细胞周期和分化相关基因的表达的影响，包括上调p21 waf 1/cip 1和下调致癌蛋白c-Myc。汉黄芩苷还促进PLSCR 1进入细胞核，并促进其与1，4，5-三磷酸肌醇受体1（IP 3 R1）启动子的结合，从而增加IP 3 R1的表达。最后，用小干扰RNA抑制PLSCR 1表达部分阻断了汉黄芩苷诱导的细胞周期停滞和分化，并扰乱了汉黄芩苷相关的分子事件。因此，本研究的结果表明，汉黄芩苷可能代表治疗AML的治疗候选者。
Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the anticancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted antiproliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through the induction of G1 phase arrest and the promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle-and differentiation-related genes, including the upregulation of p21waf1/cip1 and downregulation of the oncogenic protein c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonosideassociated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML.