Source:http://linkedlifedata.com/resource/pubmed/id/15917307
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2005-9-19
|
| pubmed:abstractText |
Breast cancer resistance protein (BCRP/ABCG2) is known to actively transport various anticancer drugs and to restrict the uptake of the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine from the gut lumen. The present study reveals that BCRP is involved in the transport of phase-2 metabolites of the carcinogen benzo[a]pyrene (BP) in the human intestinal cell line Caco-2. Treatment with the selective BCRP inhibitor Ko 143 (5 microM) inhibited the apical transport of BP-3-sulfate (BP3S) to 83% of control levels in TC7 cells and to 64% of control levels in Caco-2 cells. The apical transport of BP-3-glucuronide was inhibited by Ko 143 to 76% of control levels in TC7 cells. Furthermore, the expression of BCRP is most likely aryl hydrocarbon receptor (AhR) dependent, as treatment of Caco-2 cells with known AhR agonists including 2,3,7,8-tetrachlorodibenzo-p-dioxin, BP, indolo[3,2-b]carbazole and benzo[k]fluoranthene increased both mRNA and protein levels of BCRP. Induced BCRP protein was found to be functionally active, since pre-treatment of TC7 cells with oltipraz, indolo[3,2-b]carbazole or benzo[k]fluoranthene increased the amount of apically transported BP3S to as much as 180% of that in the controls. The induction of BCRP (mRNA and protein expression) by indolo[3,2-b]carbazole was inhibited in Caco-2 cells by co-incubation with the AhR antagonist PD98059 (2'-amino-3'-methoxyflavone). In summary, this study provides strong evidence that BCRP is an important part of the intestinal barrier protecting the body from food-associated contaminants such as the carcinogen BP.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Anticarcinogenic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon,
http://linkedlifedata.com/resource/pubmed/chemical/Reserpine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin,
http://linkedlifedata.com/resource/pubmed/chemical/oltipraz
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0143-3334
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
26
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1754-63
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:15917307-ATP-Binding Cassette Transporters,
pubmed-meshheading:15917307-Adenocarcinoma,
pubmed-meshheading:15917307-Anticarcinogenic Agents,
pubmed-meshheading:15917307-Benzo(a)pyrene,
pubmed-meshheading:15917307-Biological Transport,
pubmed-meshheading:15917307-Cell Line, Tumor,
pubmed-meshheading:15917307-Colonic Neoplasms,
pubmed-meshheading:15917307-Enzyme Inhibitors,
pubmed-meshheading:15917307-Flavonoids,
pubmed-meshheading:15917307-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:15917307-Humans,
pubmed-meshheading:15917307-Kinetics,
pubmed-meshheading:15917307-Neoplasm Proteins,
pubmed-meshheading:15917307-Pyrazines,
pubmed-meshheading:15917307-RNA, Messenger,
pubmed-meshheading:15917307-Receptors, Aryl Hydrocarbon,
pubmed-meshheading:15917307-Reserpine,
pubmed-meshheading:15917307-Tetrachlorodibenzodioxin
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Identification of BCRP as transporter of benzo[a]pyrene conjugates metabolically formed in Caco-2 cells and its induction by Ah-receptor agonists.
|
| pubmed:affiliation |
Institute for Food Toxicology, University of Veterinary Medicine Hannover, Foundation, Bischofsholern Damm 15/115, 30173 Hannover, Germany.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|