ToxSci Advance Access originally published online on October 31, 2006
Toxicological Sciences 2007 96(2):227-236; doi:10.1093/toxsci/kfl147
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Phytochemicals Induce Breast Cancer Resistance Protein in Caco-2 Cells and Enhance the Transport of Benzo[a]pyrene-3-sulfate
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* Institute for Food Toxicology, School of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Germany
Biochemical Institute for Environmental Carcinogens, Prof. Dr Gernot Grimmer Foundation, 22927 Grosshansdorf, Germany
Department of Food Safety, Federal Institute of Risk Assessment, 14195 Berlin, Germany
1 To whom correspondence should be addressed at Department of Food Safety, Federal Institute of Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany. Fax: (+49) 30 84 12 3685. E-mail: a.lampen{at}bfr.bund.de.
Received August 9, 2006; accepted October 9, 2006
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Abstract |
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We have previously reported that breast cancer resistance protein (BCRP) is involved in the transport of phase II 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 tert-butyl hydroquinone (TBHQ) for their effects on BCRP expression. In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100µM), dibenzoylmethane (DBM, 50µM), and quercetin (25µM), while green tea component (–)-epicatechin (50µM) decreased BCRP 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 wild-type 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 activators sulforaphane and diethylmaleate (DEM) had no inducing effect on BCRP mRNA expression. Caco-2 cells pretreated with quercetin or DBM showed an enhancement of apically transported benzo[a]pyrene-3-sulfate, indicating that induced BCRP 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 procarcinogens such as BP.
Key Words: BCRP; benzo[a]pyrene; quercetin; dibenzoylmethane; phytochemicals; Caco-2 cells.
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  M. Wang Extending the Good Diet, Good Health Paradigm: Modulation of Breast Cancer Resistance Protein (BCRP) by Flavonoids Toxicol. Sci., April 1, 2007; 96(2): 203 - 205. [Full Text] [PDF]
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