Diverging role of Nrf2 in cancer progression and prevention

Abstract

The role of transcription factor, nuclear factor [erythroid-derived 2]-like 2 (Nrf2), is detoxification of xenobiotics, overcoming oxidative stress and offering resistance to ionizing radiation induced cell death. However, the role of Nrf2 in cancer progression remains debatable. Activation of Nrf2 dependent proteins is crucial in maintaining cellular redox homeostasis and combating toxicity of carcinogens. Thus, employing natural or synthetic activators of Nrf2 pathway is a promising approach for development of chemopreventive modalities. Intriguingly, recent reports have highlighted the dark side of Nrf2 suggesting that multiple cancer cells demonstrate constitutive activation of Nrf2 caused by mutations in Nrf2 or Keap-1 proteins, offering survival advantage. Additionally, Nrf2 pathway is also up-regulated in chemoresistant cells and may be a major contributor in acquired chemoresistance. Thus, targeting Nrf2 pathway has emerged as a novel strategy to improve efficacy of chemotherapeutic drugs. This review discusses the dark and bright sides of this transcription factor in line with the recent literature.

Keywords

• cancer
• nrf-2 transcription factor
• keap-1 protein
• β-trcp protein