NF-κB and Nrf2 as potential chemopreventive targets of some anti-inflammatory and antioxidative phytonutrients with anti- inflammatory and antioxidative activities

Abstract

Chemoprevention refers to the use of defined non-toxic chemical regimens to inhibit, reverse or retard the process of multi-stage carcirrogenesis that involves multiple signal transduction events. A new horizon in chemoprevention research is the recent discovery of molecular links between inflammation and cancer. Components of the cell signaling network, especially those that converge on the ubiquitous eukaryotic redox-sensitive transcription factor, nuclear factor-kappa B (NF-kappa B), have been implicated in the pathogenesis of many inflammation-associated disorders. A wide variety of chemopreventive and chemoprotective phytochemicals and phytonutrients can alter or correct undesired cellular functions caused by abnormal pro-inflammatory signal transmissions, mediated by NF-kappa B. Modulation of cellular signaling involved in chronic inflammatory responses, induced by anti-inflammatory agents, hence provides a rational and pragmatic strategy in molecular target-based chemoprevention and cytoprotection. Induction of phase-2 detoxifying or antioxidant genes represents an important cellular defence in response to oxidative and electrophilic insults. Nuclear transcription factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) plays a crucial role in regulating phase-2 detoxifying/antioxidant gene induction. Many antioxidants derived from dietary and medicinal plants have been found to activate this particular redox-sensitive transcription factor, thereby potentiating the cellular antioxidant or detoxification capacity.