The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells
The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells
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DOI：
10.1007/s10495-005-1878-z
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发表时间：
2005-05-01
期刊：
影响因子：
7.2
通讯作者：
Redfern, CRF
中科院分区：
文献类型：
--
作者：
Hewson, QDC;Lovat, PE;Redfern, CRF
芬维A胺通过涉及活性氧（ROS）产生、12-脂氧合酶活性和GADD 153转录因子诱导的信号通路诱导SH-SY 5 Y神经母细胞瘤细胞凋亡。NF-κ B是许多细胞信号传导途径的关键元件，并在不同的细胞类型中发挥促凋亡或抗凋亡作用。研究表明，NF-κ B可能在SH-SY 5 Y细胞中起促凋亡作用，并且在其他细胞类型中，NF-κ B活化可能与脂氧合酶活性相关。本研究的目的是验证NF-κ B B活性介导芬维A胺诱导的SH-SY 5 Y神经母细胞瘤细胞凋亡的假设。使用一个显性负构I κ B α稳定转染到SH-SY 5 Y细胞，我们表明，细胞凋亡，但不是诱导活性氧，响应芬维A胺被阻断废除NF-κ B活性。在亲本SH-SY 5 Y细胞中，芬维A胺诱导NF-κ B活性和I κ B α磷酸化。这些结果表明NF-κ B活性将芬维A胺诱导的ROS与SH-SH 5 Y细胞的凋亡诱导联系起来，并且可能是未来开发神经母细胞瘤治疗药物的靶点。
Fenretinide induces apoptosis in SH-SY5Y neuroblastoma cells via a signaling pathway involving the production of reactive oxygen species (ROS), 12-lipoxygenase activity and the induction of the GADD153 transcription factor. NF-kappa B is a key element of many cell signaling pathways and adopts a pro- or anti-apoptotic role in different cell types. Studies have suggested that NF-kappa B may play a pro-apoptotic role in SH-SY5Y cells, and in other cell types NF-kappa B activation may be linked to lipoxygenase activity. The aim of this study was to test the hypothesis that NF-kappa B activity mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Using a dominant-negative construct for I kappa B alpha stably transfected into SH-SY5Y cells, we show that apoptosis, but not the induction of ROS, in response to fenretinide was blocked by abrogation of NF-kappa B activity. In parental SH-SY5Y cells, fenretinide induced NF-kappa B activity and I kappa B alpha phosphorylation. These results suggest that NF-kappa B activity links fenretinide-induced ROS to the induction of apoptosis in SH-SH5Y cells, and may be a target for the future development of drugs for neuroblastoma therapy.