Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression
Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression
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姜黄素通过 Nrf2 介导的 Fen1 表达下调抑制乳腺癌细胞增殖
DOI：
10.1016/j.jsbmb.2014.01.009
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发表时间：
2014-09-01
影响因子：
4.1
通讯作者：
Xu, Zihui
中科院分区：
文献类型：
--
作者：
Chen, Bin;Zhang, Youzhi;Xu, Zihui
姜黄素可抑制乳腺癌细胞增殖，但其抑制机制尚不清楚。Flap核酸内切酶1（Fen 1）是一种DNA修复特异性核酸酶，其过表达与乳腺癌的发生有关。nrf 2是细胞抗氧化防御系统的主要调节因子。姜黄素可诱导非乳腺癌细胞和乳腺癌细胞中Nrf 2的表达。然而，姜黄素诱导的乳腺癌细胞增殖的抑制是否可能涉及Nrf 2介导的Fen 1表达尚不清楚。在这项研究中，我们证明姜黄素抑制Fen 1依赖的MCF-7细胞增殖，并显着诱导Nrf 2蛋白表达，同时抑制Fen 1蛋白表达。姜黄素能以Nrf 2依赖的方式下调Fen 1基因的表达。进一步的研究表明，姜黄素可以导致Nrf 2从细胞质易位到细胞核，并通过减少Nrf 2向Fen 1启动子的募集来降低Fen 1启动子的活性。提示姜黄素可能通过Nrf 2介导的Fen 1表达下调抑制乳腺癌细胞增殖，这可能是姜黄素抑制肿瘤生长的一种新机制。(C)2014爱思唯尔有限公司版权所有。
Curcumin can inhibit cell proliferation of breast cancer, but the mechanism for this inhibition remains unclear. Over-expression of Flap endonuclease 1 (Fen1), a DNA repair-specific nuclease, is involved in the development of breast cancer. Nrf2 is a master regulator of cellular antioxidant defense systems. Curcumin can induce the expression of Nrf2 in both non-breast cancer cells and breast cancer cells. However, whether curcumin-induced inhibition of breast cancer cell proliferation may involve Nrf2-mediated Fen1 expression is not yet understood. In this study, we demonstrated that curcumin inhibited Fen1 -dependent proliferation of MCF-7 cells and significantly induced Nrf2 protein expression while inhibiting Fen1 protein expression. Curcumin could down-regulate Fen1 gene expression in a Nrf2-dependent manner. Further investigation revealed that curcumin could lead to Nrf2 translocation from the cytoplasm to the nucleus and decrease Fen1 promoter activity by decreasing the recruitment of Nrf2 to the Fen1 promoter. These data suggest that curcumin may inhibit the proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen1 expression, which may be a new mechanism of curcumin-induced tumor growth inhibition. (C) 2014 Elsevier Ltd. All rights reserved.