Nrf2 in human cancers: biological significance and therapeutic potential

Abstract

The nuclear factor-erythroid 2-related factor 2 (Nrf2) is able to control the redox balance in the cells responding to oxidative damage and other stress signals. The Nrf2 upregulation can elevate the levels of antioxidant enzymes to support against damage and death. In spite of protective function of Nrf2 in the physiological conditions, the stimulation of Nrf2 in the cancer has been in favour of tumorigenesis. Since the dysregulation of molecular pathways and mutations/deletions are common in tumors, Nrf2 can be a promising therapeutic target. The Nrf2 overexpression can prevent cell death in tumor and by increasing the survival rate of cancer cells, ensures the carcinogenesis. Moreover, the induction of Nrf2 can promote the invasion and metastasis of tumor cells. The Nrf2 upregulation stimulates EMT to increase cancer metastasis. Furthermore, regarding the protective function of Nrf2, its stimulation triggers chemoresistance. The natural products can regulate Nrf2 in the cancer therapy and reverse drug resistance. Moreover, nanostructures can specifically target Nrf2 signaling in cancer therapy. The current review discusses the potential function of Nrf2 in the proliferation, metastasis and drug resistance. Then, the capacity of natural products and nanostructures for suppressing Nrf2-mediated cancer progression is discussed.