Rutgers, The State University of New Jersey, Ernest Mario School of Pharmacy, Department of Pharmaceutics, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Expert Opin Ther Targets. 2011 Mar;15(3):281-95. doi: 10.1517/14728222.2011.553602. Epub 2011 Jan 25.
Numerous epidemiological studies have linked consumption of cruciferous vegetables to a reduced risk of colorectal cancer (CRC) in individuals. It is currently well accepted that chronic inflammation is a contributing factor in 15 - 20% malignancies including CRC. Many chemopreventive compounds are effective in preclinical systems and many ongoing clinical trials are showing promising findings. Many of these compounds could activate the antioxidant responsive element (ARE), a critical regulatory element for Phase II protective/detoxification and antioxidative stress enzymes mediated by nuclear factor-erythroid 2-related factor 2 (Nrf2). Recently, Nrf2 has emerged as a novel target for the prevention of CRC.
A full literature search was performed using PubMed with the key words 'ARE, Nrf2, colon, colorectal cancer, chemoprevention, cancer prevention', and all relevant publications are included.
The use of Nrf2 knockout mice has provided key insights into the toxicological and chemopreventive importance of this pathway. Mounting evidence has revealed that Nrf2 is a critical regulator of inflammation as well, a major driving force for CRC progression and formation. Targeting the Nrf2/ARE pathway may present a novel therapeutic approach for the treatment of not only colorectal inflammatory diseases but the frequent subsequent development of CRC as well.
许多流行病学研究表明,十字花科蔬菜的消费与结直肠癌(CRC)风险降低有关。目前人们普遍认为,慢性炎症是包括 CRC 在内的 15-20%恶性肿瘤的一个促成因素。许多化学预防化合物在临床前系统中有效,许多正在进行的临床试验正在显示出有希望的结果。这些化合物中的许多可以激活抗氧化反应元件(ARE),这是核因子-红细胞 2 相关因子 2(Nrf2)介导的 II 期保护/解毒和抗氧化应激酶的关键调节元件。最近,Nrf2 已成为预防 CRC 的一个新靶点。
使用 PubMed 进行了全面的文献检索,关键词为“ARE、Nrf2、结肠、结直肠癌、化学预防、癌症预防”,并包括所有相关出版物。
使用 Nrf2 基因敲除小鼠为该途径的毒理学和化学预防重要性提供了重要的见解。越来越多的证据表明,Nrf2 也是炎症的关键调节剂,是 CRC 进展和形成的主要驱动力。靶向 Nrf2/ARE 途径可能为不仅治疗结直肠炎症性疾病,而且为经常随后发生的 CRC 提供一种新的治疗方法。