Inhibitory effects of various beverages on the sulfoconjugation of 17β-estradiol in human colon carcinoma caco-2 cells

To investigate the possible effects of different beverages in the gastrointestinal tract on the sulfation of estrogen, which is a major hormone and prototype substrate for the human sulfotransferases (SULT), we analyzed the effects of these substances upon the sulfate conjugation of 17β-estradiol (E₂) in the human colon carcinoma cell line Caco-2. Sulfoconjugation activity toward E₂ was measured by incubating 20 nM E₂ with Caco-2 cells in the presence (5% (v/v)) of each beverage. Among the 35 beverages analyzed, four (aronia, blueberry, coffee, and peppermint) exhibited strong inhibitory effects on E₂ sulfation within Caco-2 cells (IC₅₀ values ranging from 1.9 to 4.4% (v/v)). These active beverages also strongly inhibited the cytosolic estrogen SULT activity of Caco-2 cells in vitro (IC₅₀ values ranging from 0.18 to 0.3% (v/v)). These inhibitory activities were extractable with ethyl acetate but not hexane or n-butanol, indicating that the molecules responsible are moderately lipophilic. Coffee was found to be the most potent inhibitor but the major constituents of this beverage, caffeic acid, caffeine, and chlorogenic acid, did not show any effects on estrogen SULT activity. Kinetic analyses further indicated that the mode of inhibition by coffee is competitive. A possible relationship between the inhibition of estrogen SULT activity by coffee in the gastrointestinal tract and the reported reduction of colon cancer incidence in women who consume coffee is discussed.