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A Potential Chemopreventive Agent, Taxifolin, Upregulates Phase II Detoxification Enzymes Through Antioxidant Response Element
Author(s) -
Lee Saet Byoul,
Cha Kwang Hyun,
Selenge D,
Solongo A,
Nho Chu Won
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1014-d
Subject(s) - taxifolin , detoxification (alternative medicine) , enzyme , chemistry , biochemistry , downregulation and upregulation , antioxidant , gene , medicine , alternative medicine , flavonoid , pathology
Phase II detoxification enzymes are known to be responsible for detoxification and elimination of activated carcinogens suggesting that induction of these enzymes is an important biomarker for chemoprevention. In this study, we have tested chemopreventive activity of taxifolin, a flavanon compound purified from mongolian medicinal plant, using quinone reductase (QR) activity in HCT 116 cells. Taxifolin significantly induced QR activity while it showed relatively low cytotoxicity in the cells (chemoprevention index = 5.74). In order to identify the target genes regulated by taxifolin, cDNA microarray was performed using 3K human cancer chip containing 3000 human genes associated with carcinogenesis. According to significant analysis of microarray (SAM), 428 DE genes were found to be statistically significant with false discovery rate (FDR) of 57.2% (delta = 0.3366). Sixty five genes including few detoxification enzymes (NQO1, GST‐M1, TXNRD1) were up‐regulated and 363 genes were down‐regulated in the presence of 60 μM taxifolin. Since the genes of interest selected contained antioxidant response element (ARE) located in the promoter region of detoxification enzymes, we hypothesized that taxifolin may act through ARE for upregulation of phase II detoxification enzymes. Transient transfection experiments using pARE‐CAT construct showed that taxifolin activated ARE significantly while it did not activate XRE. In conclusion, these results suggest that taxifolin is a novel monofunctional inducer upregulating only phase II enzymes through ARE, implicating that taxifolin could be a potential chemopreventive agent.