Nrf2-two faces of antioxidant system regulation

Abstract

One of the most prominent defense mechanisms of cells undergoing stress is the Nrf2-Keap signaling pathway. After exposure to either carcinogens or toxic compounds inducing oxida-tive stress, attacked cells react by release of Keapl from the Nrf2-Keap1 complex. Freeing Nrf from the complex allows its translocation into the nucleus, thus enabling start of the transcriptional program of cytoprotective genes. Therefore, induction of Nrf2 by chemopreventive compounds may show potential in cancer prevention. But while it protects normal cells, increase activity of Nrf2 signaling pathway also facilitates cancer progression and protects neoplastic cells from therapeutic agents. Increased expression and subsequent accumulation of Nrf2 contributes to acquired drug resistance and is often associated with worse prognosis. Knowing 'both faces' of Nrf2 signaling pathway is thus relevant not only for basic research but has als substantial clinical implications.