Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways
- Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways
- 윤지호; 이샛별; 이희주; 김철영; 김미애; 손영창; 노주원
- youngiaside; quinone reductase; cytochrome P450 1A1; bi-functional inducer; cancer chemoprevention
- Issue Date
- Biological & pharmaceutical bulletin
- VOL 33, NO 10, 1650-1657
- Many phytochemicals are known to exert cancer chemopreventive activity by eliminating chemical carcinogens
or toxic xenobiotics through the action of detoxification enzymes. In this study, we investigated the cancer
chemopreventive effects of youngiasides isolated from Crepidiastrum denticulatum. These youngiasides significantly
induced quinone reductase (QR) activity in mouse hepatoma Hepa-1c1c7 cells, and showed a relatively
high chemoprevention index (CI; divided IC50 value with CD value). The youngiasides also significantly induced
transcriptional activation of QR in Hepa-QR-secreted alkaline phosphatase (SEAP) cells, which is a stable cell
line containing the intact promoter region of QR. In order to determine if upregulation of QR by the youngiasides
was mediated through a mono-functional or bi-functional mechanism, we examined the nuclear factor-E2
p45-related factor 2(Nrf2)-antioxidant response element (ARE) and aryl hydrocarbon receptor (AhR)-xenobiotic
response element (XRE) pathways, which are two major pathways, involved in regulation of Phase I and/or
Phase II detoxification enzymes. The youngiasides increased the cytochrome P450 1A1 (CYP1A1) mRNA and
protein levels in human colorectal cancer Caco-2 cells and also increased the QR mRNA and protein levels in
Caco-2 cells through ARE and XRE activation which resulted from translocation of Nrf2 and AhR into the nucleus.
These results suggest that regulation of QR by the youngiasides was due to bi-functional induction through
the Nrf2-ARE and AhR-XRE pathways. Thus, these youngiasides as bi-functional inducers of QR have potential
as cancer chemopreventive agents.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.