title: Pomegranate juice inhibits sulfoconjugation in Caco-2 human colon carcinoma cells.
abstract: Several fruit juices have been reported to cause food-drug interactions, mainly affecting cytochrome P450 activity; however, little is known about the effects of fruit juices on conjugation reactions. Among several fruit juices tested (apple, peach, orange, pineapple, grapefruit, and pomegranate), pomegranate juice potently inhibited the sulfoconjugation of 1-naphthol in Caco-2 cells. This inhibition was both dose- and culture time-dependent, with a 50% inhibitory concentration (IC(50)) value calculated at 2.7% (vol/vol). In contrast, no obvious inhibition of glucuronidation of 1-naphthol in Caco-2 cells was observed by any of the juices examined. Punicalagin, the most abundant antioxidant polyphenol in pomegranate juice, was also found to strongly inhibit sulfoconjugation in Caco-2 cells with an IC(50) of 45 microM, which is consistent with that of pomegranate juice. These data suggest that punicalagin is mainly responsible for the inhibition of sulfoconjugation by pomegranate juice. We additionally demonstrated that pomegranate juice and punicalagin both inhibit phenol sulfotransferase activity in Caco-2 cells in vitro, at concentrations that are almost equivalent to those used in the Caco-2 cells. Pomegranate juice, however, shows no effects on the expression of the sulfotransferase SULT1A family of genes (SULT1A1 and SULT1A3) in Caco-2 cells. These results indicate that the inhibition of sulfotransferase activity by punicalagin in Caco-2 cells is responsible for the reductions seen in 1-naphthyl sulfate accumulation. Our data also suggest that constituents of pomegranate juice, most probably punicalagin, impair the enteric functions of sulfoconjugation and that this might have effects upon the bioavailability of drugs and other compounds present in food and in the environment. These effects might be related to the anticarcinogenic properties of pomegranate juice.
authors.affiliation: Kyoritsu University of Pharmacy, Minatoku, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Saruwatari
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Okamura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Narukawa
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Takeda
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology; D001628:Beverages; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000378:metabolism*; D018565:Food-Drug Interactions / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects; D029561:Lythraceae; D050216:Metabolic Detoxication, Phase I; D009284:Naphthols / Q000493:pharmacokinetics; D009363:Neoplasm Proteins / Q000187:drug effects; D028321:Plant Preparations; D015238:Sulfotransferases / Q000187:drug effects
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000975:Antioxidants; D047348:Hydrolyzable Tannins; D009284:Naphthols; D009363:Neoplasm Proteins; D028321:Plant Preparations; C115642:punicalagin; D015238:Sulfotransferases