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首页> 外文期刊>The Journal of Nutritional Biochemistry >EGR-1/Bax pathway plays a role in vitamin E delta-tocotrienol-induced apoptosis in pancreatic cancer cells
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EGR-1/Bax pathway plays a role in vitamin E delta-tocotrienol-induced apoptosis in pancreatic cancer cells

机译：EGR-1 / Bax通路在维生素Eδ-生育三烯酚诱导的胰腺癌细胞凋亡中起作用

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摘要

The anticancer activity of delta-tocotrienol, a bioactive vitamin E present in whole grain cereals, annatto beans and palm fruit, is strongly dependent on its effect on the induction of apoptosis. delta-Tocotrienol-induced apoptosis is associated with consistent induction in the expression of the proapoptotic protein BcI-2-associated X protein (Bax). The molecular mechanism by which delta-tocotrienol regulates Bax expression is unknown. We carried out a DNA microarray study that identified delta-tocotrienol induction of the zinc finger transcription factor EGR-1 in pancreatic cancer cells. Here, we provide evidence linking delta-tocotrienol-induced apoptosis in pancreatic cancer cells to EGR-1 regulation of Bax expression. Forced expression of EGR-1 induces Bax expression and apoptosis in pancreatic cancer cells. In contrast, knockdown of delta-tocotrienol-induced EGR-1 by small interfering RNA attenuated delta-tocotrienol-induced Bax expression and reduced delta-tocotrienol-induced apoptosis. Further analyses showed that de nova protein synthesis was not required for delta-tocotrienol-induced EGR-1 expression, suggesting a direct effect of delta-tocotrienol on EGR-1 expression. Furthermore, a chromatin immunoprecipitation assay demonstrated that EGR-1 binds to the Bax gene promoter. Finally, delta-tocotrienol treatment induced Bax expression and activated EGR-1 in the pancreatic neoplastic cells of the PDX-Cre Kras genetically engineered model of pancreatic cancer. Our study provides the first evidence for EGR-1 as a direct target of vitamin E delta-tocotrienol, suggesting that EGR-1 may act as a proapoptotic factor in pancreatic cancer cells via induction of Bax. (C) 2015 Elsevier Inc. All rights reserved.
机译：三角洲生育三烯酚（一种存在于全谷类谷物，安纳托豆和棕榈果中的生物活性维生素E）的抗癌活性在很大程度上取决于其对诱导细胞凋亡的作用。 δ-生育三烯酚诱导的凋亡与促凋亡蛋白Bcl-2关联的X蛋白（Bax）表达的持续诱导有关。 δ-生育三烯酚调节Bax表达的分子机制尚不清楚。我们进行了DNA芯片研究，该研究确定了胰腺癌细胞中锌指转录因子EGR-1的δ-生育三烯酚诱导作用。在这里，我们提供了证据，将δ-生育三烯酚诱导的胰腺癌细胞凋亡与Bax表达的EGR-1调节联系起来。 EGR-1的强迫表达诱导胰腺癌细胞中Bax表达和凋亡。相反，通过小的干扰RNA敲低δ-生育三烯酚诱导的EGR-1减弱了δ-生育三烯酚诱导的Bax表达并减少了δ-生育三烯酚诱导的细胞凋亡。进一步的分析表明，δ-生育三烯酚诱导的EGR-1表达不需要新蛋白合成，这表明δ-生育三烯酚对EGR-1表达具有直接作用。此外，染色质免疫沉淀试验证明EGR-1与Bax基因启动子结合。最后，δ-生育三烯酚处理可在PDX-Cre Kras基因工程胰腺癌模型的胰腺肿瘤细胞中诱导Bax表达并激活EGR-1。我们的研究为EGR-1作为维生素Eδ-生育三烯酚的直接靶标提供了第一个证据，表明EGR-1可能通过诱导Bax充当胰腺癌细胞的促凋亡因子。 （C）2015 Elsevier Inc.保留所有权利。

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