Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation
Styryl-lactone goniothalamin inhibits TNF-α-induced NF-κB activation
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DOI：
10.1016/j.fct.2013.06.051
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发表时间：
2013-09-01
影响因子：
4.3
通讯作者：
Diederich, Marc
中科院分区：
文献类型：
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作者：
Orlikova, Barbora;Schumacher, Marc;Diederich, Marc
(R)-(+)-蛇床子内酯(GTN)是从药用植物大叶海棠中分离得到的一种苯乙酰内酯，具有细胞毒性和抗炎等药理活性。在本研究中，GTN调节了肿瘤坏死因子-α诱导的核因子-kappaB的激活。GTN在20 mU M以下对K562慢性粒细胞白血病和Jurkat T细胞有较低的细胞毒作用。重要的是，在这些浓度下，没有观察到健康外周血单核细胞的细胞毒性。报告基因分析和免疫印迹显示，GTN在低至5mM的浓度下可抑制肿瘤坏死因子-α(TNF-α)诱导的Jurkat和K562白血病细胞中核因子-kappaB的激活。此外，GTN下调p50/p65异二聚体到细胞核的转位，阻止核因子-kappa B与其DNA反应元件结合，并减少肿瘤坏死因子-α激活的白细胞介素8(IL-8)的表达。总之，在不同的白血病细胞模型中，GTN在非致凋亡浓度下抑制了肿瘤坏死因子-α诱导的核因子-kappaB的激活，而对健康的血细胞没有毒性，这突显了这种天然化合物的抗白血病潜力。(C)2013爱思唯尔有限公司。保留所有权利。
(R)-(+)-Goniothalamin (GTN), a styryl-lactone isolated from the medicinal plant Goniothalamus macrophyllus, exhibits pharmacological activities including cytotoxic and anti-inflammatory effects. In this study, GTN modulated TNF-alpha induced NF-kappa B activation. GTN concentrations up to 20 mu M showed low cytotoxic effects in K562 chronic myelogenous leukemia and in Jurkat T cells. Importantly, at these concentrations, no cytotoxicity was observed in healthy peripheral blood mononuclear cells. Our results confirmed that GTN inhibited tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappa B activation in Jurkat and K562 leukemia cells at concentrations as low as 5 mu M as shown by reporter gene assays and western blots. Moreover, GTN down-regulated translocation of the p50/p65 heterodimer to the nucleus, prevented binding of NF-kappa B to its DNA response element and reduced TNF-alpha-activated interleukin-8 (IL-8) expression. In conclusion, GTN inhibits TNF-alpha-induced NF-kappa B activation at non-apoptogenic concentrations in different leukemia cell models without presenting toxicity towards healthy blood cells underlining the anti-leukemic potential of this natural compound. (C) 2013 Elsevier Ltd. All rights reserved.