NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells
NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells
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DOI：
10.1007/s10495-006-0576-9
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发表时间：
2007-02-01
期刊：
影响因子：
7.2
通讯作者：
Kwon, T. K.
中科院分区：
文献类型：
--
作者：
Lim, J. H.;Park, J-W.;Kwon, T. K.
槲皮素是一种广泛存在于自然界中的类黄酮分子，对癌细胞具有多种作用，包括抑制细胞增殖和迁移。然而，负责的分子机制尚未完全理解。我们发现，槲皮素诱导的HCT 116人结肠癌细胞凋亡过程中，槲皮素诱导表达NAG-1（非甾体抗炎药激活基因-1），TGF-β超家族蛋白。使用含有NAG-1启动子区的荧光素酶构建体的报告基因测定证明，早期生长反应-1（EGR-1）和p53是槲皮素介导的NAG-1启动子激活所必需的。NAG-1的过表达增强了槲皮素的凋亡作用，但NAG-1 siRNA抑制槲皮素诱导的NAG-1表达减弱了槲皮素诱导的HCT 116细胞凋亡。综上所述，本研究首次证明槲皮素通过NAG-1诱导细胞凋亡，为槲皮素诱导结肠癌细胞凋亡提供了机制基础。
Quercetin, a flavonoid molecule ubiquitously present in nature, has multiple effects on cancer cells, including the inhibition of cell proliferation and migration. However, the responsible molecular mechanisms are not fully understood. We found that quercetin induces the expression of NAG-1 (Non-steroidal anti-inflammatory drug activated gene-1), a TGF-beta superfamily protein, during quercetin-induced apoptosis of HCT116 human colon carcinoma cells. Reporter assays using the luciferase constructs containing NAG-1 promoter region demonstrate that early growth response-1 (EGR-1) and p53 are required for quercetin-mediated activation of the NAG-1 promoter. Overexpression of NAG-1 enhanced the apoptotic effect of quercetin, but suppression of quercetin-induced NAG-1 expression by NAG-1 siRNA attenuated quercetin-induced apoptosis in HCT116 cells. Taken together, the present study demonstrates for the first time that quercetin induces apoptosis via NAG-1, providing a mechanistic basis for the apoptotic effect of quercetin in colon carcinoma cells.