3--4--dimethoxyflavone and Esophageal-Neoplasms

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.

Topics: Aryl Hydrocarbon Hydroxylases; Benzo(a)pyrene; Blotting, Western; Cell Line; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; DNA; DNA Adducts; Esophageal Neoplasms; Flavones; Flavonoids; Gene Expression Regulation, Enzymologic; Humans; RNA, Messenger; Time Factors