Lim J H, Park J-W, Min D S, Chang J-S, Lee Y H, Park Y B, Choi K S, Kwon T K
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong, Taegu, 700-712, Korea.
Apoptosis. 2007 Feb;12(2):411-21. doi: 10.1007/s10495-006-0576-9.
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.
槲皮素是一种在自然界中普遍存在的类黄酮分子，对癌细胞有多种作用，包括抑制细胞增殖和迁移。然而，其具体的分子机制尚未完全明确。我们发现，在槲皮素诱导HCT116人结肠癌细胞凋亡的过程中，槲皮素可诱导TGF-β超家族蛋白NAG-1（非甾体抗炎药激活基因-1）的表达。使用含有NAG-1启动子区域的荧光素酶构建体进行的报告基因检测表明，早期生长反应因子-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表达会减弱槲皮素诱导的HCT116细胞凋亡。综上所述，本研究首次证明槲皮素通过NAG-1诱导凋亡，为槲皮素在结肠癌细胞中的凋亡作用提供了机制基础。
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