Yun, Ji Ho Lee, Saet Byoul Lee, Hee Ju Kim, Chul Young Kim, Mi Ae Sohn, Young Chang Nho, Chu Won 2024-01-20T18:32:03Z 2024-01-20T18:32:03Z 2021-09-05 2010-10 0918-6158 https://pubs.kist.re.kr/handle/201004/131046 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 H 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. English PHARMACEUTICAL SOC JAPAN ARYL-HYDROCARBON RECEPTOR TRANSCRIPTIONAL REGULATION REGULATORY MECHANISMS SIGNALING PATHWAYS GENE-EXPRESSION PHASE-I ENZYMES IDENTIFICATION OLTIPRAZ DIETARY Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways Article 10.1248/bpb.33.1650 1 BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.33, no.10, pp.1650 - 1657 BIOLOGICAL & PHARMACEUTICAL BULLETIN 33 10 1650 1657 scie scopus 000282420300003 2-s2.0-77958006952 Pharmacology & Pharmacy Pharmacology & Pharmacy Article ARYL-HYDROCARBON RECEPTOR TRANSCRIPTIONAL REGULATION REGULATORY MECHANISMS SIGNALING PATHWAYS GENE-EXPRESSION PHASE-I ENZYMES IDENTIFICATION OLTIPRAZ DIETARY youngiaside quinone reductase cytochrome P450 1A1 bi-functional inducer cancer chemoprevention