title: The licorice flavonoid isoliquiritigenin reduces DNA-binding activity of AhR in MCF-7 cells.
abstract: Licorice is derived from the rhizomes of Glycyrrhiza glabra. It has been used for confectioneries or culinary purposes. The rhizomes contain many flavonoidal compounds that have been shown to be biologically active. In the present study, effect of the licorice flavonoid isoliquiritigenin (ILN) on polycyclic aromatic hydrocarbon (PAH)-induced XRE transactivation and the downstream expression were investigated in MCF-7 cells. The environmental toxicant PAHs are pro-carcinogens and are biotransformed into their ultimate genotoxic structures by cytochrome P450 (CYP) 1 enzymes. Reporter gene assay revealed that ILN reduced XRE transactivation triggered by 7,12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-Tetrachlorodibenzodioxin (TCDD). Our EMSA results also demonstrated that the flavonoid diminished DMBA-induced XRE binding. The reduced transactivation could be the result of a decreased amount of AhR translocating from cytosol to nucleus as shown in Western analysis. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay demonstrated that expressions of genes with XRE-containing promoters, including CYP1A1, 1A2, and 1B1, followed the same pattern of XRE transactivation. The present study illustrated that ILN might downregulate PAH-induced expressions through antagonizing AhR translocation.
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Food Science, National Chiayi University, Chiayi City, Taiwan.
authors.forename: Shu-mei
authors.initials: SM
authors.lastname: Lin
authors.affiliation: Molecular Biotechnology Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors.forename: Ching Ho
authors.initials: CH
authors.lastname: Poon
authors.affiliation: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. Electronic address: laikleung@cuhk.edu.hk.
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D047188:Chalcones / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047188:Chalcones; D004785:Environmental Pollutants; D005419:Flavonoids; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D004247:DNA; C040920:isoliquiritigenin; D001189:Aryl Hydrocarbon Hydroxylases
keywords: 2,3,7,8-Tetrachlorodibenzodioxin; 7,12-dimethylbenz[a]anthracene; AHR; AhR; CYP1 family enzymes; DMBA; EROD; FBS; Isoliquiritigenin; Licorice; PAH; TCDD; XRE; aryl hydrocarbon receptor; ethoxyresorufin-O-deethylase; fetal bovine serum; polycylic aromatic hydrocarbon; xenobiotic response element