Skip Navigation



ToxSci Advance Access published online on October 31, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl147
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
96/2/227    most recent
kfl147v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ebert, B.
Right arrow Articles by Lampen, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ebert, B.
Right arrow Articles by Lampen, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 9, 2006
Accepted October 9, 2006

Biotransformation and Toxicokinetics

Phytochemicals induce BCRP in Caco-2 Cells and Enhance the Transport of Benzo[a]pyrene-3-sulfate

Bettina Ebert 1, Albrecht Seidel 2, and Alfonso Lampen 1 *

1 Department of Food Safety, Federal Institute of Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany
2 Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer Foundation, Lurup 4, 22927 Grosshansdorf, Germany

* To whom correspondence should be addressed.
Alfonso Lampen, E-mail: a.lampen{at}bfr.bund.de


  Abstract

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 µM), dibenzoylmethane (DBM, 50 µM) and quercetin (25 µM), while green tea component (-)-epicatechin (50 µM) 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.

Keywords: BCRP; benzo[a]pyrene; quercetin; dibenzoylmethane; phytochemicals; Caco-2 cells.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
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]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.