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Broccoli alters estrogen metabolism in favor of 2‐methoxyestradiol in vitro
Author(s) -
Volker Sonja E,
Jeffery Elizabeth H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.720.5
Subject(s) - chemistry , 2 methoxyestradiol , metabolism , biochemistry , estrogen , nad+ kinase , incubation , in vitro , microsome , enzyme , biology , endocrinology
An increased 2‐hydroxy:16alpha‐hydroxy estrogen ratio may be correlated with reduced breast cancer risk. Estrogens are hydroxylated at the C‐2 position by cytochrome P450 1A (CYP1A). 2‐Hydroxyestrogens can be methylated by catechol‐ O ‐methyltransferase to form antitumorigenic 2‐methoxyestrogens, or can be oxidized to quinones that may react with DNA. Quinones may be reduced back to 2‐hydroxyestrogens by NAD(P)H:quinone oxidoreductase (NQO1). Broccoli contains glucosinolates that, upon hydrolysis, form bioactive isothiocyanates, which are known inducers of CYP1A and NQO1. Aqueous extracts of freeze‐dried broccoli powders were generated through overnight hydrolysis at room temperature (50 mg/mL water). Incubation of mouse hepatoma Hepa‐1c1c7 cells with broccoli extracts for 24 h induced CYP1A and NQO1 activities up to 72 and 4.9‐fold, respectively. When Hepa‐1c1c7 cells were incubated with 10 μM estradiol in the absence of broccoli extracts, no 2‐methoxyestradiol formation was observed by HPLC‐MS/MS. In contrast, a 24 h exposure of cells to broccoli extracts, followed by 24 h simultaneous exposure to broccoli extracts and 10 μM estradiol lead to formation of measurable amounts of 2‐methoxyestradiol in the culture medium. These results indicate that broccoli may redirect estrogen metabolism toward formation of anti‐tumorigenic 2‐methoxyestradiol, through induction of CYP1A and NQO1 activity. (supported by grants from USDA and NIH)