The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Gonçalves P (Author) FMUP; Gregório, Maria João (Author) FCNAUP; Martel, F (Author) FMUP

Journal

Title: American Journal of Physiology - Cell Physiology

Vol. 301

Pages: C984-C994

ISSN: 0363-6143

Publisher: American Physiological Society

Indexing

ISI Web of Knowledge - 24 Citations

Scopus - 27 Citations

Other information

Authenticus ID: P-002-K4F

DOI: 10.1152/ajpcell.00146.2011

Abstract (EN): Goncalves P, Gregorio I, Martel F. The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein. Am J Physiol Cell Physiol 301: C984-C994, 2011. First published July 20, 2011; doi:10.1152/ajpcell.00146.2011.-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 C-14-BT and H-3-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 C-14-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 C-14-BT efflux in IEC-6 cells, both BT and BCRP inhibitors significantly decreased the efflux of the known BCRP substrate H-3-folic acid in IEC-6 cells, and BCRP inhibitors reduced C-14-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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11