Oxidative Stress, Nrf2, and Epigenetic Modification Contribute to Anticancer Drug Resistance
نویسندگان
چکیده
Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.
منابع مشابه
Molecular basis of electrophilic and oxidative defense: promises and perils of Nrf2.
Induction of drug-metabolizing enzymes through the antioxidant response element (ARE)-dependent transcription was initially implicated in chemoprevention against cancer by antioxidants. Recent progress in understanding the biology and mechanism of induction revealed a critical role of induction in cellular defense against electrophilic and oxidative stress. Induction is mediated through a novel...
متن کاملVersatile activity of the master regulator of the antioxidant response in tumor initiation, progression and metastasis
Oxidative intermediates derived from endogenous metabolism or xenobiotic stimuli are a major cause of cancer initiation. Host defense systems have evolved to cope with these oxidative stresses and prevent carcinogenesis. The basic leucine zipper transcription factor Nrf2 (Nuclear factor-erythroid derived 2-like 2, Nfe2l2) regulates the cellular defense system against oxidative stress, and gover...
متن کاملRedox Modulating NRF2: A Potential Mediator of Cancer Stem Cell Resistance
Tumors contain a distinct small subpopulation of cells that possess stem cell-like characteristics. These cells have been called cancer stem cells (CSCs) and are thought to be responsible for anticancer drug resistance and tumor relapse after therapy. Emerging evidence indicates that CSCs share many properties, such as self-renewal and quiescence, with normal stem cells. In particular, CSCs and...
متن کاملThe Role of Epigenetics in Cancer Drug Resistance
Cancer is caused by aberrant genetic and epigenetic changes in genes expression. DNA methylation, histone modification, and microRNAs gene deregulation are the most known epigenetic changes in different stages of cancer. Since every tumor has its own specific epigenome, any abnormal pattern is a potential biomarker for classification of different types of tumors. Despite, tumorigenesis, abnorma...
متن کاملNatural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases.
Covering: 2000 to 2013. Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural prod...
متن کامل