Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells
Curcumin regulates signal transducer and activator of transcription (STAT) expression in K562 cells
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DOI：
10.1016/j.bcp.2006.07.029
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发表时间：
2006-11-30
影响因子：
5.8
通讯作者：
Diederich, Marc
中科院分区：
文献类型：
--
作者：
Blasius, Romain;Reuter, Simone;Diederich, Marc
信号转导和转录激活因子(STATs)在许多细胞事件中发挥重要作用，如分化、炎症或免疫反应。此外，在大量的肿瘤中可以观察到结构性STAT的激活。在我们的手中，姜黄素诱导K562细胞中核STAT3、-5a和-5b的表达减少，但不影响STAT1，也不影响STAT1、-3或-5的磷酸化状态。最有趣的是，姜黄素处理后核STAT5a和-5b的减少伴随着截短的STAT5亚型的增加，这表明姜黄素能够诱导STAT5切割成其缺乏STAT5 C-末端区域的显性负变异体。干扰素-β和-γ处理可诱导干扰素刺激的反应元件(ISRE)转录活性，而姜黄素可有效抑制其转录活性。同时，干扰素-γ诱导核STAT1和-3及其磷酸化异构体的数量增加。再一次，姜黄素预处理抑制了这些增加。姜黄素可抑制K562慢性白血病细胞JAK2基因的表达以及细胞周期蛋白d1和v-src基因的表达。(C)2006 Elsevier Inc.保留所有权利。
Signal transducers and activators of transcription (STATs) play important roles in numerous cellular events as for example differentiation, inflammation or immune response. Furthermore, constitutive STAT activation can be observed in a high number of tumors. In our hands, curcumin treatment induced a decrease of nuclear STAT3, -5a and -5b, without affecting neither STAT1, nor the phosphorylation state of STAT1, -3 or -5 in the K562 cell line. Most interestingly, the decrease of nuclear STAT5a and -5b after curcumin treatment was accompanied by an increase of truncated STAT5 isoforms, indicating that curcumin is able to induce the cleavage of STAT5 into its dominant negative variants lacking the STAT5 C-terminal region. Interferon (IFN)-beta and -gamma treatment induced IFN-stimulated responsive element (ISRE) transcriptional activity, which was efficiently inhibited by curcumin pretreatment. In parallel, IFN-gamma treatment induced an increase of the amount of nuclear STAT1 and -3, as well as their phosphorylated isoforms. Again, curcumin pre-treatment inhibited these increases. Finally, curcumin treatment inhibited Jak2 mRNA expression as well as cyclin D1 and v-src gene expression in K562 chronic leukaemia cells. (c) 2006 Elsevier Inc. All rights reserved.