Phytochemicals induce BCRP in Caco-2 Cells and Enhance the Transport of Benzo[a]pyrene-3-sulfate
2006
Ebert, B. | Seidel, A. | Lampen, A.
Немецкий. We have previously reported that breast cancer resistance protein (BCRP) is involved in the transport of phase-2 metabolites of the food carcinogen benzo[a]pyrene (BP) in the human intestinal cell line Caco-2. Furthermore, the expression of BCRP seemed most likely to be aryl hydrocarbon receptor (AhR)-dependent. Since numerous plant-derived anticarcinogens with AhR-agonistic activity have been identified to date, in the present study we investigated the effects of naturally occurring dietary compounds and t-butyl hydroquinone (TBHQ) for their effects on BCRP expression. In Caco-2 cells, the most pronounced induction of BCRP protein expression could be observed after treatment with TBHQ (100 microM), dibenzoylmethane (DBM, 50 microM) and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP protein expression. On mRNA level, quercetin, chrysin, flavone and indole-3-carbinol showed a strong inducing effect, while genistein had no effect on BCRP mRNA expression. Curcumin and resveratrol showed a strong effect on BCRP induction in MCF-7 WT cells but no response in AhR-deficient MCF-7AHR200 cells, supporting our hypothesis that BCRP is regulated via AhR-dependent signaling pathways. Inhibition of proteasome-mediated degradation of ligand-activated AhR caused a "superinduction" of BCRP mRNA. Antioxidant responsive element (ARE)-activators sulforaphane and diethylmaleate (DEM) had no inducing effect on BCRP mRNA expression. Caco-2 cells pre-treated with quercetin or DBM showed an enhancement of apically transported BP-3-sulfate, indicating that induced BCRP protein was functionally active. In conclusion, apart from the modulation of detoxifying enzymes in the intestine, induction of BCRP by dietary constituents may contribute to the detoxification of food-derived pro-carcinogens such as BP
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Издатель Oxford University Press
ISSN 1096-6080 | 1096-0929Эту запись предоставил German Federal Institute for Risk Assessment