The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation(Molecular and Cell Biology)

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概要

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• Phase II detoxification enzymes are responsible for the detoxification and elimination of activated carcinogens, and thus act as important biomarkers for chemoprevention. In this study, we tested the chemopreventive activity of taxifolin, a flavanon compound purified from a mongolian medicinal plant, by measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced significant QR activity, but displayed relatively low cytotoxicity in cells (chemoprevention index=5.75). To identify the target genes regulated by taxifolin, DNA microarray was performed with a 3K human cancer chip containing 3096 human genes associated with carcinogenesis. Significant analysis of microarray (SAM) revealed 428 differentially expressed (DE) genes as statistically significant, with a false discovery rate (FDR) of 57.2% (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (NQO1, GSTM1) and an antioxidant enzyme (TXNRD1), were up-regulated and 363 genes were down-regulated in the presence of 60 jUM taxifolin. In view of the finding that selected genes of interest contained antioxidant response element (ARE), we hypothesize that taxifolin modulates chemopreventive genes through activation of the ARE. Transient transfection experiments using the ARE QR-CAT construct demonstrate that taxifolin significantly activates ARE, but not xenobiotic response element (XRE). In conclusion, taxifolin acts as a potential chemopreventive agent by regulating genes via an ARE-dependent mechanism.

• 2007-06-01

著者

• Nho Chu

  Natural Products Research Center, Gangneung Institute, Korea Institute of Science and Technology

• Nho Chu

  Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.

• Cha Kwang

  Natural Products Research Center Korea Institute Of Science And Technology

• LEE Saet

  Natural Products Research Center, Korea Institute of Science and Technology

• SELENGE Dangaa

  Institute of Chemical and Chemical Technology

• SOLONGO Amgalan

  Institute of Chemical and Chemical Technology

• Lee Saet

  Natural Products Res. Center Gangneung Inst. Korea Inst. Of Sci. And Technol.

関連論文

• Bi-Functional Induction of the Quinone Reductase and Cytochrome P450 1A1 by Youngiasides via Nrf2-ARE and AhR-XRE Pathways
• The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation(Molecular and Cell Biology)
• The Chemopreventive Effects of Saussurea salicifolia through Induction of Apoptosis and Phase II Detoxification Enzyme(Pharmacognosy)

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