Sex hormone modulation of both induction and inhibition of CYP1A by genistein in HepG2/C3A cells

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 t...

Full description

Saved in:
Bibliographic Details
Published in:In vitro cellular & developmental biology. Animal 2015-04, Vol.51 (4), p.426-431
Main Authors: Liu, Yitong, Santillo, Michael F., Flynn, Thomas J., Ferguson, Martine S.
Format: Article
Language:English
Subjects:
Animal Genetics and Genomics
Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors
Aryl Hydrocarbon Hydroxylases - metabolism
Benzoflavones - pharmacology
beta-Naphthoflavone - pharmacology
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP1A2 - genetics
Developmental Biology
Female
Gene Expression Regulation, Enzymologic - drug effects
Genistein - pharmacology
Gonadal Steroid Hormones - pharmacology
Hep G2 Cells - drug effects
Humans
Life Sciences
Male
Stem Cells
Testosterone - pharmacology
TOXICOLOGY/CHEMICAL CARCINOGENESIS
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1071-2690
1543-706X
DOI:10.1007/s11626-014-9848-9