Dual roles of Nrf2 in cancer.

Dual roles of Nrf2 in cancer.
复制标题

DOI:
10.1016/j.phrs.2008.09.003
复制
发表时间:
2008-11
影响因子:
9.3
通讯作者:
Zhang, Donna D.
Zhang, Donna D.
中科院分区:
医学1区
文献类型:
--
作者:
Lau, Alexandria;Villeneuve, Nicole F.;Sun, Zheng;Wong, Pak Kin;Zhang, Donna D.

文献摘要

参考文献

被引文献

相似文献

在氧化应激反应中,转录因子NF-E2相关因子2(Nrf 2)通过转录上调抗氧化反应元件(ARE)基因(包括编码内源性抗氧化剂、II相解毒酶和转运蛋白的基因)来控制细胞的命运。Nrf 2依赖性蛋白的表达对于改善或消除毒物/致癌物以维持细胞氧化还原稳态是至关重要的。因此,通过天然存在的化合物或合成化学品以亚毒性剂量激活Nrf 2途径,可提供针对随后的毒性/致癌性暴露的保护。因此,使用膳食化合物或合成化学品来促进Nrf 2依赖性适应性反应以抵消环境损伤已经成为预防癌症的有希望的策略。有趣的是,最近出现的数据揭示了Nrf 2的“黑暗”一面。Nrf 2及其下游基因在许多癌细胞系和人类癌组织中过表达,使癌细胞具有生存和生长的优势。此外,Nrf 2在耐药癌细胞中上调,并被认为是获得性化疗耐药性的原因。因此,在化疗期间抑制Nrf 2通路可能是必要的。本文就Nrf 2在肿瘤中的作用作一综述,重点介绍近年来Nrf 2的促癌作用及其在获得性耐药中的作用。
In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing genes, including those encoding endogenous antioxidants, phase II detoxifying enzymes, and transporters. Expression of the Nrf2-dependent proteins is critical for ameliorating or eliminating toxicants/carcinogens to maintain cellular redox homeostasis. As a result, activation of the Nrf2 pathway, by naturally-occurring compounds or synthetic chemicals at sub-toxic doses, confers protection against subsequent toxic/carcinogenic exposure. Thus, the use of dietary compounds or synthetic chemicals to boost the Nrf2-dependent adaptive response to counteract environmental insults has emerged to be a promising strategy for cancer prevention. Interestingly, recent emerging data has revealed the “dark” side of Nrf2. Nrf2 and its downstream genes are overexpressed in many cancer cell lines and human cancer tissues, giving cancer cells an advantage for survival and growth. Furthermore, Nrf2 is upregulated in resistant cancer cells and is thought to be responsible for acquired chemoresistance. Therefore, it may be necessary to inhibit the Nrf2 pathway during chemotherapy. This review is primarily focused on the role of Nrf2 in cancer, with emphasis on the recent findings indicating the cancer promoting function of Nrf2 and its role in acquired chemoresistance.
DOI: 10.1016/s0167-4781(00)00238-4
发表时间: 2000-12-15
期刊: BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子: --
作者:
Chan, JY;Kwong, M
通讯作者: Kwong, M
多药耐药相关蛋白 1 (MRP1) 介导的长春新碱耐药性:N-乙酰半胱氨酸和丁硫氨酸亚磺酰亚胺的作用。
DOI: 10.1186/1475-2867-5-22
发表时间: 2005-07-24
影响因子: 5.8
作者:
Akan I;Akan S;Akca H;Savas B;Ozben T
通讯作者: Ozben T
DOI: 10.1073/pnas.93.24.13943
发表时间: 1996-11-26
影响因子: 11.1
作者:
Chan, KM;Lu, RH;Kan, YW
通讯作者: Kan, YW
DOI: 10.1042/bj20021619
发表时间: 2003-05-01
影响因子: 4.1
作者:
Balogun, E;Hoque, M;Motterlini, R
通讯作者: Motterlini, R
DOI: 10.1016/j.freeradbiomed.2004.07.021
发表时间: 2004-11-15
影响因子: 7.4
作者:
Chen, C;Pung, D;Kong, ANT
通讯作者: Kong, ANT