Gymnasterkoreayne B induces activation of Nuclear factor-E2 (Nrf2) through phosphorylation by ERK1/2 and PKC kinase
- Gymnasterkoreayne B induces activation of Nuclear factor-E2 (Nrf2) through phosphorylation by ERK1/2 and PKC kinase
- 이경미; 강경수; 김미애; 윤지호; 노주원
- Phytochemicals; Gymnasterkoreayne B
- Issue Date
- 생화학분자생물학회 (KSBMB)
- Phytochemicals are well known to have cancer chemopreventive effects by induction of phase II detoxification enzymes including quinone reductase (QR) and HO-1. As one of candidates for phytochemicals, we recently identified Gymnasterkoreayne B (GKB) isolated from Gymnaster(Aster) Koraiensis. Our previous study showed that GKB induces QR activity in mouse hepatoma Hepa-1c1c7 cells, and a relatively high chemoprevention index representing high QR activity with a low cytotoxicity. In this study, we confirmed that GKB significantly increases expression levels of Nrf2 in human colon cancer HCT 116 cells. To investigate which upstream signaling pathways have an effect on activation of Nrf2 by GKB, we examined changes of various kinases in HCT 116 cells treated with GKB. We observed that phosphorylation by various kinases plays an important role in increasing Nrf2 levels and stability. Furthermore, we found that ERK and PKC pathways are specially involved in the activation of Nrf2 by GKB, followed by translocation of Nrf2 and induction of QR. These results suggest that the GKB induces phase II detoxification enzymes by forming phospho-Nrf2 through activating ERK and PKC in HCT 116 cells.
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