Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells.
Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells.
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DOI：
10.3390/cancers13123022
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发表时间：
2021-06-16
期刊：
影响因子：
5.2
通讯作者：
Baek SJ
中科院分区：
文献类型：
--
作者：
Hong Y;Lee J;Moon H;Ryu CH;Seok J;Jung YS;Ryu J;Baek SJ
甲状腺癌是世界上最常见的癌症之一，其发病率在过去几十年里有所上升。不同类型的甲状腺癌很难诊断。甲状腺乳头状癌组织中成熟NAG-1高表达，而癌旁正常组织中高表达。几种抗癌化合物可增加甲状腺癌细胞中NAG-1原的表达。栎素(3，3‘，4’，5，7-五羟基黄酮)是一种类黄酮类化合物，是树莓、葡萄和洋葱等多种植物的主要成分。在转录因子C/EBP的作用下，仅诱导原NAG-1的表达，而不诱导成熟NAG-1的表达，从而诱导细胞凋亡。本研究表明，原NAG-1可以作为一种有用的甲状腺癌生物标志物，也为槲皮素治疗甲状腺癌提供了一个潜在的治疗靶点。尽管甲状腺癌的治疗有所改善，但由于缺乏特定的诊断和预后标志，不必要的手术仍然存在。因此，在甲状腺癌的诊断和治疗中应考虑寻找新的生物标志物。在这项研究中，利用甲状腺乳头状癌患者的肿瘤和邻近正常组织进行抗体阵列，并确定了几个潜在的生物标志物。在根据抗体阵列数据选择的候选蛋白中，成熟的NAG-1在肿瘤组织中的表达高于邻近的正常组织。相反，蛋白质印迹分析显示，正常组织中原NAG-1的表达增加。此外，当植物化学物质和非甾体抗炎药以剂量依赖的方式处理甲状腺癌细胞时，原NAG-1的表达增加。尤其是，槲皮素高诱导原NAG-1的表达，但不诱导成熟NAG-1的表达，具有增强的抗癌活性，包括诱导细胞凋亡和细胞周期停滞。对NAG-1启动子活性的检测表明，P53、C/eBPα或C/eBPδ在Quercetin诱导的NAG-1表达中起作用。总体而言，我们的研究表明，NAG-1可能作为一种新的甲状腺癌预后的生物标志物，并可能被用作甲状腺癌的治疗靶点。
Thyroid cancer is one of the most common cancers worldwide, and its incidence has increased over the last few decades. It is difficult to diagnose different types of thyroid cancer. Tumor tissues from papillary thyroid cancer patient showed higher expression of mature NAG-1, whereas adjacent normal tissues showed higher expression of pro-NAG-1. Several anti-cancer compounds increased pro-NAG-1 expression in thyroid cancer cell line. Quercetin (3,3’,4’,5,7-pentahydroxyflavone) is a flavonoid that is a major component of various plants, including raspberries, grapes, and onions. Quercetin induced apoptosis by inducing only pro-NAG-1 expression, but not mature NAG-1, mediated by the transcription factor C/EBP. This study indicates that pro-NAG-1 could be used as a useful biomarker for thyroid cancer and also provides a potential therapeutic target for the treatment of thyroid cancer with quercetin. Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.
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DOI：
10.1016/j.jnutbio.2012.03.016
发表时间：
2013-04
期刊：
The Journal of nutritional biochemistry
影响因子：
--
作者：
Lee SH;Min KW;Zhang X;Baek SJ
通讯作者：
Baek SJ
影响因子：
8
作者：
Giordano, TJ;Kuick, R;Nikiforov, YE
通讯作者：
Nikiforov, YE
影响因子：
2
作者：
Hisaka, Toru;Sakai, Hisamune;Yano, Hirohisa
通讯作者：
Yano, Hirohisa
影响因子：
8
作者：
Lee, S-H;Bahn, J. H.;Whitlock, N. C.;Baek, S. J.
通讯作者：
Baek, S. J.
影响因子：
5.6
作者：
Lee, Seong-Ho;Richardson, Raphael L.;Dashwood, Roderick H.;Baek, Seung Joan
通讯作者：
Baek, Seung Joan