title: An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy.
abstract: The Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes in response to oxidative and xenobiotic stress. A large number of Nrf2-antioxidant response element (ARE) activators have been screened for use as chemopreventive agents in oxidative stress-related diseases and even cancer. However, constitutive activation of Nrf2 occurs in a variety of cancers. Aberrant activation of Nrf2 is correlated with cancer progression, chemoresistance, and radioresistance. In this review, we examine recent studies of Nrf2-ARE inhibitors in the context of cancer therapy. We enumerate the possible Nrf2-inhibiting mechanisms of these compounds, their effects sensitizing cancer cells to chemotherapeutic agents, and the prospect of applying them in clinical cancer therapy.
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Road, Heping Area, Shenyang 110001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Fu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China. Electronic address: yyxu@cmu.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Kou
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhai
authors.affiliation: MedBlue Incubator, Inc., Research Triangle Park, NC 27709, USA.
authors.forename: M Bud
authors.initials: MB
authors.lastname: Nelson
authors.affiliation: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, ScitoVation, LLC, NC 27709, USA LLC.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Andersen
authors.affiliation: Program of Environmental Toxicology, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China. Electronic address: jbpi@cmu.edu.cn.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Pi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D061745:Antioxidant Response Elements / Q000187:drug effects*; D000995:Antitubercular Agents / Q000494:pharmacology; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000072019:Kelch-Like ECH-Associated Protein 1 / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction; D014815:Vitamins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; C503645:CUL3 protein, human; D044842:Cullin Proteins; D005419:Flavonoids; D007004:Hypoglycemic Agents; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D014815:Vitamins
keywords: ARE; Cancer therapy; Chemoresistance; Inhibitor; Nrf2