Nrf2-ARE signaling pathway and natural products for cancer chemoprevention

Background: One of the potential strategies for preventing cancers is using food-based natural products to induce cytoprotective enzymes including phase II and antioxidative enzymes that act in concert to detoxify and eliminate harmful reactive intermediates formed from carcinogens. The antioxidant response element (ARE), which is activated upon binding of the nuclear factor E2-related protein 2 (Nrf2) transcription factor protein, has been identified in the regulatory regions of numerous genes encoding cytoprotective enzymes. Herein, we summarized the current body of knowledge regarding Nrf2 regulation as well as highlighted the Nrf2/ARE activators from natural products, which will potentially be used as chemopreventive agents for cancer patients. Methods: Via reviewing Pubmed, we summarized the current progress in the molecular mechanisms of Nrf2 regulation and the major classes of dietary components that act as promising chemopreventive agents through evoking Nrf2-ARE core signaling pathway. Results: Under basal condition, Nrf2 is at low level, sequestered in the cytoplasm by being tethered to an actin binding Kelch-like ECH associating protein 1 (Keap1). Pharmacological and putative chemopreventive agents trigger the release of Nrf2 from Keap1, allowing it to translocate into the nucleus and drive the gene expression of detoxifying enzymes to perform cancer chemoproventive effect. Conclusion: Augmenting both expression and activity of phase II detoxification and antioxidant enzymes via Nrf2-ARE core signaling pathway would be a rational approach for cancer chemoprevention and the number of novel Nrf2/ARE activators from dietary sources is growing. (C) 2010 Elsevier Ltd. All rights reserved.