Arsenic trioxide represses constitutive activation of NF-κB and COX-2 expression in human acute myeloid leukemia, HL-60
Arsenic trioxide represses constitutive activation of NF-κB and COX-2 expression in human acute myeloid leukemia, HL-60
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DOI：
10.1002/jcb.20337
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发表时间：
2005-03-01
影响因子：
4
通讯作者：
Park, S
中科院分区：
文献类型：
--
作者：
Han, SS;Kim, K;Park, S
有人提出，真核核转录因子核因子kappa-B (NF-kappaB) 和环氧合酶-2 (COX-2) 与包括癌症在内的许多人类疾病的发病机制有关。砷在东方国家已广泛用于医药。最近的研究表明，三氧化二砷(AS(2)O(3))可以在体外诱导恶性淋巴细胞和骨髓瘤细胞的生长抑制和凋亡。然而，AS(2)O(3) 启动细胞信号传导至细胞死亡的分子机制仍不清楚。在本研究中，研究了AS(2)O(3)对HL-60细胞中NF-κB和COX-2表达的影响。 AS(2)O(3)通过阻止IkappaB-α的降解和随后p65的核转位以及中断NF-kappaB与其共有序列的结合来抑制由p65/p50异二聚体组成的NF-kappaB的DNA结合活性。 AS(2)O(3) 对 NF-kappaB DNA 活性的抑制作用取决于细胞内谷胱甘肽 (GSH) 和 H2O2 水平，而不是超氧阴离子。此外，我们发现AS(2)O(3)还通过抑制NF-kappaB DNA结合活性下调COX-2的表达，COX-2的启动子上有NF-kappaB结合位点。 (C) 2004 Wiley-Liss, Inc.
It has been proposed that eukaryotic nuclear transcripton factor nuclear factor kappa-B (NF-kappaB) and cyclooxygenase-2 (COX-2) are implicated in the pathogenesis of many human diseases including cancer. Arsenic has been widely used in medicine in Oriental countries. Recent studies have shown that arsenic trioxide (AS(2)O(3)) Could induce in vitro growth inhibition and apoptosis of malignant lymphocytes, and myeloma cells. However, the molecular mechanisms by which AS(2)O(3) initiates cellular signaling toward cell death are still unclear. In the present study, the effects of AS(2)O(3) on NF-kappaB and COX-2 expression in HL-60 cells were investigated. AS(2)O(3) suppressed DNA-binding activity of NF-kappaB composed of p65/p50 heterodimer through preventing the degradation of IkappaB-alpha and the nuclear translocation of p65 subsequently as well as interrupting the binding of NF-kappaB with their consensus sequences. Inhibitory effect of AS(2)O(3) on NF-kappaB DNA activity was dependent upon intracellular glutathione (GSH) and H2O2 level, but not superoxide anion. Furthermore, we found that AS(2)O(3) also downregulated the expression of COX-2, which has NF-kappaB binding site on its promoter through repressing the NF-kappaB DNA-binding activity. (C) 2004 Wiley-Liss, Inc.