title: 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.
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.
authors: Leibniz Research Institute for Environmental Medicine (IUF), Auf'm Hennekamp 50, 40225 Düsseldorf, Germany.
authors: Hanno
authors: H
authors: Bothe
authors: Kathrin
authors: K
authors: Gassmann
authors: Christine
authors: C
authors: Götz
authors: Ellen
authors: E
authors: Fritsche
authors: Josef
authors: J
authors: Abel
authors: Thomas
authors: T
authors: Haarmann-Stemmann
mesh_terms: D001564:Benzo(a)pyrene / Q000378:metabolism*; D001711:Biotransformation; D018938:Caco-2 Cells; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D044948:Flavonols; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors*; D000099148:UGT1A1 Enzyme
chemical_list: D001564:Benzo(a)pyrene; D002392:Catechin; D019363:Cytochrome P-450 CYP1A1; D005419:Flavonoids; D044948:Flavonols; D014453:Glucuronosyltransferase; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D000099148:UGT1A1 Enzyme; C045651:epigallocatechin gallate; C017875:fisetin