Abstract
Esophageal cancer is common worldwide, with poor prognosis. Smoking, including exposure to polyaromatic hydrocarbons like benzo[a]pyrene (BaP), is a major risk factor. In human esophageal HET-1A cells, we found that time-dependent BaP-DNA binding was associated with upregulation of CYP1B1, but not CYP1A1, mRNA and protein. The dietary flavonoid 5,7-dimethoxyflavone significantly inhibited BaP-DNA binding and down-regulated BaP-induced CYP1B1 mRNA and protein. 3',4'-Dimethoxyflavone was an even more potent inhibitor of CYP1B1 expression, while resveratrol had no effect. Thus, dietary methoxylated flavones inhibited BaP-induced CYP1B1 transcription in a cell-specific manner and hold promise as chemopreventive agents in esophageal carcinogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
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Aryl Hydrocarbon Hydroxylases / genetics*
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Aryl Hydrocarbon Hydroxylases / metabolism
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Benzo(a)pyrene / metabolism
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Benzo(a)pyrene / pharmacology*
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Blotting, Western
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Cell Line
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Cytochrome P-450 CYP1A1 / genetics
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Cytochrome P-450 CYP1A1 / metabolism
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Cytochrome P-450 CYP1B1
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DNA / metabolism
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DNA Adducts
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Esophageal Neoplasms / chemically induced
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Esophageal Neoplasms / enzymology
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Esophageal Neoplasms / prevention & control
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Flavones / pharmacology
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Flavones / therapeutic use
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Flavonoids / pharmacology
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Flavonoids / therapeutic use
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Gene Expression Regulation, Enzymologic / drug effects
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Humans
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Time Factors
Substances
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3',4'-dimethoxyflavone
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DNA Adducts
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Flavones
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Flavonoids
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RNA, Messenger
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5,7-dimethoxyflavone
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Benzo(a)pyrene
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DNA
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Aryl Hydrocarbon Hydroxylases
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CYP1B1 protein, human
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Cytochrome P-450 CYP1A1
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Cytochrome P-450 CYP1B1