Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways

Title
Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways
Authors
윤지호이샛별이희주김철영김미애손영창노주원
Keywords
youngiaside; quinone reductase; cytochrome P450 1A1; bi-functional inducer; cancer chemoprevention
Issue Date
2010-10
Publisher
Biological & pharmaceutical bulletin
Citation
VOL 33, NO 10, 1650-1657
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/45584
ISSN
0918-6158
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KIST Publication > Article
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