title: Mechanisms of Nrf2/Keap1-dependent phase II cytoprotective and detoxifying gene expression and potential cellular targets of chemopreventive isothiocyanates.
abstract: Isothiocyanates (ITCs) are abundantly found in cruciferous vegetables. Epidemiological studies suggest that chronic consumption of cruciferous vegetables can lower the overall risk of cancer. Natural ITCs are key chemopreventive ingredients of cruciferous vegetables, and one of the prime chemopreventive mechanisms of natural isothiocyanates is the induction of Nrf2/ARE-dependent gene expression that plays a critical role in cellular defense against electrophiles and reactive oxygen species. In the present review, we first discuss the underlying mechanisms how natural ITCs affect the intracellular signaling kinase cascades to regulate the Keap1/Nrf2 activities, thereby inducing phase II cytoprotective and detoxifying enzymes. We also discuss the potential cellular protein targets to which natural ITCs are directly conjugated and how these events aid in the chemopreventive effects of natural ITCs. Finally, we discuss the posttranslational modifications of Keap1 and nucleocytoplasmic trafficking of Nrf2 in response to electrophiles and oxidants.
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Gyeonggi-do 410-820, Republic of Korea.
authors.forename: Biswa Nath
authors.initials: BN
authors.lastname: Das
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
mesh_terms: D000818:Animals; D018890:Chemoprevention; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017879:Isothiocyanates / Q000494:pharmacology*; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C037152:isothiocyanic acid