Nrf2-Keap1 signaling as a common chemopreventive target of antioxidative and anti-inflammatory phytochemicals

Abstract

A precise and timely regulation of redox balance is essential for the cellular homeostatic control. Nuclear factor erythroid derived 2-related factor-2 (Nrf2) is a transcription factor that mediates cellular defense mechanism against oxidative stress by neutralizing electrophiles or reactive oxygen species. However, recent studies have revealed that Nrf2 also has an anti-inflammatory function and hence represents an important therapeutic target for the inflammatory disorders. Thus, disruption of cellular defense response by Nrf2 deficiency has been found to cause enhanced susceptibility to not only oxidative stress but also inflammatory injuries. Although it has not been clearly elucidated, the antioxidative function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the expression of proinflammatory genes. Many dietary phytonutrients can induce Nrf2-mediated cytoprotective gene expression, thereby fortifying cellular defense against oxidative and inflammatory insult. Therefore, the maintenance of cellular defense capacity through activation of Nrf2 represents an important mechanism underlying chemoprevention of oxidative stress-and inflammation-associated carcinogenesis.