Cytochrome P450 1B1, a novel chemopreventive target for benzo[a]pyrene-initiated human esophageal cancer.
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.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
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Wen
Thomas
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Walle
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C509288:3',4'-dimethoxyflavone; D018736:DNA Adducts; D047309:Flavones; D005419:Flavonoids; D012333:RNA, Messenger; C060298:5,7-dimethoxyflavone; D001564:Benzo(a)pyrene; D004247:DNA; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1