Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways
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概要
- 論文の詳細を見る
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.
- 日本薬学会の論文
著者
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Lee Hee
Natural Products Res. Center Korea Inst. Of Sci. And Technol. Gangneung Inst.
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Kim Chul
Natural Products Res. Center Korea Inst. Of Sci. And Technol. Gangneung Inst.
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Yun Ji
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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Lee Seat
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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Kim Mi
Faculty of Marine Bioscience and Technology, Gangnung-Wonju National University
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Sohn Young
Faculty of Marine Bioscience and Technology, Gangnung-Wonju National University
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Nho Chu
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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Lee Hee
Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.
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Nho Chu
Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.
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Lee Saet
Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.
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Kim Chul
Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.
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Lee Saet
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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Lee Hee
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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Kim Chul
Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology
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