title: Nuclear factor-E2 (Nrf2) is regulated through the differential activation of ERK1/2 and PKC α/βII by Gymnasterkoreayne B.
abstract: Phytochemicals are well known to have cancer chemopreventive effects by induction of phase II detoxification enzymes including quinone reductase (NQO-1) and glutathione-S-transferases. These detoxification enzymes are commonly regulated by nuclear factor-E2 (Nrf2), which is a representative antioxidant and cytoprotective factor involved in cancer chemoprevention. As one of the known quinone reductase (QR) inducers and Nrf2 activators, Gymnasterkoreayne B (GKB) isolated from Gymnaster (Aster) koraiensis was used to elucidate the upstream signalling pathway for Nrf2 regulation. In this study, we confirmed that GKB significantly increases expression levels of Nrf2 in HCT116 human colon cancer cells. We found the probable mechanism of upstream signalling pathways to activate Nrf2 by GKB. To reveal the pathway that affects Nrf2 translocation by GKB, we examined changes in various kinases in HCT116 cells treated with GKB. We observed that ERK and PKC pathways are particularly involved in the activation of Nrf2 by GKB, followed by translocation of Nrf2 and induction of NQO-1. These results suggest that GKB induces Nrf2 translocation and expression by differential regulation of ERK and PKC pathways in HCT116 cells.
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Kyungsu
authors.initials: K
authors.lastname: Kang
authors.forename: Saet Byoul
authors.initials: SB
authors.lastname: Lee
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho
mesh_terms: D021581:Active Transport, Cell Nucleus; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D053279:Polyynes / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000502:physiology*
chemical_list: D016588:Anticarcinogenic Agents; D051267:NF-E2-Related Factor 2; C579347:gymnasterkoreayne B; D053279:Polyynes; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3