Abstract |
Colorectal cancer is one of the most common cancers worldwide. Butyrate (BT) plays a key role in colonic epithelium homeostasis. The aim of this work was to investigate the possibility of BT being transported by P-glycoprotein (MDR1), multidrug resistance proteins (MRPs), or breast cancer resistance protein (BCRP). Uptake and efflux of (14)C-BT and (3)H-folic acid were measured in Caco-2, IEC-6, and MDA-MB-231 cell lines. mRNA expression of BCRP was detected by RT-PCR. Cell viability, proliferation, and differentiation were quantified with the lactate dehydrogenase, sulforhodamine B, and alkaline phosphatase activity assays, respectively. In both IEC-6 cells and Caco-2 cells, no evidence was found for the involvement of either MDR1 or MRPs in (14)C-BT efflux from the cells. In contrast, several lines of evidence support the conclusion that BT is a substrate of both rat and human BCRP. Indeed, BCRP inhibitors reduced (14)C-BT efflux in IEC-6 cells, both BT and BCRP inhibitors significantly decreased the efflux of the known BCRP substrate (3)H-folic acid in IEC-6 cells, and BCRP inhibitors reduced (14)C-BT efflux in the BCRP-expressing MDA-MB-231 cell line. In IEC-6 cells, combination of BT with a BCRP inhibitor significantly potentiated the effect of BT on cell proliferation. The results of this study, showing for the first time that BT is a BCRP substrate, are very important in the context of the high levels of BCRP expression in the human colon and the anticarcinogenic and anti-inflammatory role of BT at that level. So, interaction of BT with BCRP and with other BCRP substrates/inhibitors is clearly of major importance.
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Authors | Pedro Gonçalves, Inês Gregório, Fátima Martel |
Journal | American journal of physiology. Cell physiology
(Am J Physiol Cell Physiol)
Vol. 301
Issue 5
Pg. C984-94
(Nov 2011)
ISSN: 1522-1563 [Electronic] United States |
PMID | 21775706
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABCB1 protein, human
- ABCG2 protein, human
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP-Binding Cassette Transporters
- Abcg2 protein, rat
- Neoplasm Proteins
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Topics |
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(metabolism)
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP-Binding Cassette Transporters
(metabolism)
- Animals
- Breast Neoplasms
(metabolism)
- Caco-2 Cells
- Cell Differentiation
- Cell Line, Tumor
- Cell Proliferation
- Cell Survival
- Colorectal Neoplasms
(metabolism)
- Female
- Humans
- Neoplasm Proteins
(metabolism)
- Rats
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