title: The citrus flavanone naringenin suppresses CYP1B1 transactivation through antagonising xenobiotic-responsive element binding.
abstract: Exposure to environmental toxicants or exogenous oestrogen increases the risk of cancer. Some toxicants such as polycyclic aromatic hydrocarbons (PAH) undergo biotransformation to become genotoxic agents. Cytochrome p450 (CYP) 1B1 is an enzyme catalysing this transformation. Consumption of fruit and vegetables is considered to be protective against carcinogenesis, and naringenin can be found abundantly in citrus fruits. In the present study, the effect of naringenin on the regulation of CYP1B1 was investigated in MCF-7 cells. Enzyme inhibition assays revealed that naringenin inhibited CYP1B1 at or above 5 μm but not CYP1A1 activity. Quantitative PCR analysis also demonstrated that 1 μm-naringenin reduced CYP1B1 mRNA expression induced by 7,12-dimethylbenz(α)anthracene (DMBA). Further study illustrated that the suppression was at the transcriptional level. Since previous studies have shown that oestrogen response element (ERE) and xenobiotic-responsive element (XRE) are functional binding sequences in the promoter region of CYP1B1, interference of DNA binding on these two elements was pursued. Employing reporter gene assays as well as the electromobility shift assay, we verified that naringenin counteracted DMBA-induced XRE binding at − 1675. These results supported the notion that fruit consumption could be a protective measure against PAH biotransformation.
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.forename: Tsz Yan
authors.initials: TY
authors.lastname: Wong
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Miki
authors.initials: M
authors.lastname: Nakajima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001665:Binding Sites; D045744:Cell Line, Tumor; D065633:Cytochrome P-450 CYP1B1; D024202:Electrophoretic Mobility Shift Assay; D044950:Flavanones / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D044950:Flavanones; D012333:RNA, Messenger; D015262:Xenobiotics; D015127:9,10-Dimethyl-1,2-benzanthracene; D008156:Luciferases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; C005273:naringenin