Nuclear factor-erythroid 2-related factor 2 as a chemopreventive target in colorectal cancer

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords::

• ARE
• CRC
• inflammation
• Keap 1
• Nrf2
• oxidative stress
• Phase II enzymes

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