title: Assessing the effect of food mycotoxins on aromatase by using a cell-based system.
abstract: Zeranol, aflatoxin B1, zearalenone are mycotoxins that are commonly found as food contaminants. The chemical structures of zeranol and zearalenone resemble estrogen, and may disrupt hormone metabolism. The biosynthesis of estrogen is catalyzed by aromatase or CYP19. In the present study, effect of these mycotoxins on aromatase was evaluated by using 4 cell lines, i.e. the CYP19-overexpressing cells MCF-7aro, the placental cells JEG-3, the breast cells MCF-7, and the brain cells T98G. Our data indicated that zearalenone was a competitive inhibitor of aromatase with a K(i) value of 1 μM. As aromatase expression is promoter-specific and regulated by alternate splicing, we employed three cell lines for investigation. Our results showed that zearalenone and zeranol could suppress aromatase expression through promoters II and I.3. For aromatase transcription dictated by promoters I.f and I.1, the expression was not affected. Taken together, zearalenone was a potential aromatase inhibitor among the three mycotoxins tested. Furthermore, this 4-cell line approach could be employed in principle to screen for compounds inhibiting or inducing estrogen synthesis.
authors: Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong, People's Republic of China; Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors: Yanfei
authors: Y
authors: Wang
authors: Food and Nutritional Sciences Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors: Tsz Yan
authors: TY
authors: Wong
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
authors: Franky L
authors: FL
authors: Chan
authors: Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
authors: Shiuan
authors: S
authors: Chen
authors: Biochemistry Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong; 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: Lai K
authors: LK
authors: Leung
mesh_terms: D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015025:Zearalenone / Q000633:toxicity*; D015029:Zeranol / Q000633:toxicity*
chemical_list: D012333:RNA, Messenger; D015025:Zearalenone; D015029:Zeranol; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: Aflatoxin B1; Aromatase; Zearalenone; Zeranol