Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate.

Publisher: Oxford University Press Country of Publication: United States NLM ID: 9805461 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1096-6080 (Print) Linking ISSN: 10960929 NLM ISO Abbreviation: Toxicol Sci Subsets: MEDLINE

Publication: 1999- : Cary, NC : Oxford University Press
Original Publication: Orlando, FL : Academic Press, c1998-

ATP-Binding Cassette Transporters/*metabolism ; Benzo(a)pyrene/*metabolism ; Neoplasm Proteins/*metabolism ; Plant Extracts/*pharmacology; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters/genetics ; Benzo(a)pyrene/pharmacokinetics ; Biological Transport ; Caco-2 Cells ; Catechin/pharmacology ; Cell Line, Tumor ; Chalcones/pharmacology ; Flavonoids/chemistry ; Flavonoids/pharmacology ; Gene Expression/drug effects ; Humans ; Hydroquinones/pharmacology ; Indoles/pharmacology ; Isothiocyanates ; Maleates/pharmacology ; Molecular Structure ; Neoplasm Proteins/genetics ; Plant Extracts/chemistry ; Quercetin/pharmacology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/metabolism ; Resveratrol ; Silymarin/pharmacology ; Stilbenes/pharmacology ; Sulfoxides ; Thiocyanates/pharmacology ; Transfection

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 (100 microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) 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-7AHR(200) 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.

0 (ABCG2 protein, human)
0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
0 (ATP-Binding Cassette Transporters)
0 (Chalcones)
0 (Flavonoids)
0 (Hydroquinones)
0 (Indoles)
0 (Isothiocyanates)
0 (Maleates)
0 (Neoplasm Proteins)
0 (Plant Extracts)
0 (RNA, Messenger)
0 (Receptors, Aryl Hydrocarbon)
0 (Silymarin)
0 (Stilbenes)
0 (Sulfoxides)
0 (Thiocyanates)
3417WMA06D (Benzo(a)pyrene)
3CN01F5ZJ5 (chrysin)
55097-80-8 (7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide)
8R1V1STN48 (Catechin)
9IKM0I5T1E (Quercetin)
ANS7ME8OKC (dibenzoylmethane)
C11E72455F (indole-3-carbinol)
C12674942B (2-tert-butylhydroquinone)
G81WQB56OL (diethyl maleate)
GA49J4310U (sulforaphane)
Q369O8926L (Resveratrol)

Date Created: 20061102 Date Completed: 20070730 Latest Revision: 20211203

20221213

10.1093/toxsci/kfl147

17077187