title: Sex hormone modulation of both induction and inhibition of CYP1A by genistein in HepG2/C3A cells.
abstract: Genistein is a widely consumed phytoestrogen in dietary supplements and has been reported to play roles in both cancer prevention and promotion. These conflicting effects may be complicated by sex differences. Cytochrome P450 1A (CYP1A) participates in carcinogen activation and detoxification, and the enzyme may interact with genistein. Therefore, modulation of CYP1A by a combination of genistein and sex hormones could be responsible for sex differences related to cancer prevention and promotion. In the current study, a human liver cell line, HepG2/C3A, cultured in sex hormone-supplemented media was used to investigate the modulatory effect of genistein on CYP1A gene expression and activity. Genistein exerted both long-term (72 h) induction and short-term (immediate) inhibition of CYP1A activity in HepG2/C3A cells. In the long-term study, CYP1A gene expression and enzyme activity were induced to a greater extent in male hormone-supplemented cells than female ones. In the short-term study, CYP1A activity was inhibited more strongly by genistein in the male hormone-supplemented cells than in the female hormone-supplemented cells. These significant differences suggest that male hormones can modulate the effects of genistein on CYP1A gene expression and activity.
authors.affiliation: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, USA, yitong.liu@fda.hhs.gov.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Liu
authors.forename: Michael F
authors.initials: MF
authors.lastname: Santillo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Flynn
authors.forename: Martine S
authors.initials: MS
authors.lastname: Ferguson
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D013739:Testosterone / Q000494:pharmacology; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D001571:Benzoflavones; D012739:Gonadal Steroid Hormones; D013739:Testosterone; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone; D019833:Genistein; D001189:Aryl Hydrocarbon Hydroxylases; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2