Epigallocatechin-3-gallate does not affect the activity of enzymes involved in metabolic activation and cellular excretion of benzo[a]pyrene in human colon carcinoma cells |
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Authors: | Bothe Hanno Gassmann Kathrin Götz Christine Fritsche Ellen Abel Josef Haarmann-Stemmann Thomas |
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Affiliation: | a Leibniz Research Institute for Environmental Medicine (IUF), Auf’m Hennekamp 50, 40225 Düsseldorf, Germany b Department of Dermatology, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany |
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Abstract: | Benzo[a]pyrene (B[a]P) and related procarcinogens found in cigarette smoke and roasted foodstuff require metabolic activation to build mutagenic DNA adducts that may cause tumor diseases like colorectal cancer. The major B[a]P-activating enzymes belong to the cytochrome-P450 (CYP)-1 family and are regulated by the aryl hydrocarbon receptor (AhR). Previous studies have indicated that an inhibition of AhR is accompanied with a reduced metabolic activation of B[a]P and therefore may act protective against carcinogenesis. We investigated if the green tea flavonoid (−)-epigallocatechin-3-gallate (EGCG), a known AhR inhibitor, is able to influence B[a]P-metabolizing and B[a]P-transporting enzymes in human Caco-2 colon carcinoma cells. Strikingly, treatment with EGCG did neither affect constitutive and B[a]P-inducible expression of CYP1A1 and UDP-glucuronosyltransferase (UGT)-1A1 nor overall CYP1 and UGT enzyme activities, indicating that EGCG does not antagonize the AhR in Caco-2 cells. Since flavonoids were also identified to enhance the activity of B[a]P-carrying transporter, we analyzed if EGCG exposure alters cellular excretion of B[a]P conjugates. In contrast to the positive control fisetin, EGCG did not affect cellular excretion of B[a]P metabolites. Our data provide evidence that EGCG does not alter the metabolism and transport of B[a]P in Caco-2 cells, and thus may not protect against procarcinogenic food contaminants. |
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Keywords: | AhR, aryl hydrocarbon receptor B[a]P, benzo[a]pyrene BCRP, breast cancer resistance protein BP3G, B[a]P-3-glucuronide BP3S, B[a]P-3-sulfate CYP, cytochrome P450 DMSO, dimethylsulfoxide EGCG, (&minus )-epigallocatechin-3-gallate EROD, ethoxyresorufin-O-deethylase HSP90, heat-shock protein 90 PAH, polycyclic aromatic hydrocarbons UGT, UDP-glucuronosyltransferase |
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