Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells

Journal of Cellular Biochemistry
Pedro GonçalvesFátima Martel

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Epidemiological and experimental studies suggest that bile acids may play a role in CRC etiology. Our aim was to characterize the effect of the primary bile acid chenodeoxycholic acid (CDCA) upon(14) C-BT uptake in tumoral (Caco-2) and non-tumoral (IEC-6) intestinal epithelial cell lines. A 2-day exposure to CDCA markedly and concentration-dependently inhibited (14) C-BT uptake by IEC-6 cells (IC(50) = 120 µM), and, less potently, by Caco-2 cells (IC(50) = 402 µM). The inhibitory effect of CDCA upon (14) C-BT uptake did not result from a decrease in cell proliferation or viability. In IEC-6 cells: (1) uptake of (14) C-BT involves both a high-affinity and a low-affinity transporter, and CDCA acted as a competitive inhibitor of the high-affinity transporter; (2) CDCA inhibited both Na(+)-coupled monocarboxylate cotransporter 1 (SMCT1)- and H(+)-coupled monocarboxylate transporter 1 (MCT1)-mediated uptake of (14) C-BT; (3) CDCA significantly increased the mRNA expression level of SMCT1; (4) inhibition of (14) C-BT uptake by CDCA was dependent on CaM, MAP kinase (ERK1/2 and p38 pathways), and PKC activation, and reduced by a reactive oxygen species scavenger. Fina...Continue Reading

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Jul 22, 2011·American Journal of Physiology. Cell Physiology·Pedro GonçalvesFátima Martel
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Citations

Jul 15, 2015·Nutrition Research Reviews·Kristin A VerbekeKieran M Tuohy
Dec 4, 2012·European Journal of Pharmacology·Pedro GonçalvesFátima Martel
Mar 20, 2019·Journal of Cellular Physiology·Gang WangXing-Li Fu
Sep 28, 2020·The AAPS Journal·Jingcheng XiaoPeng Zou
Jul 1, 2016·Porto Biomedical Journal·Pedro Gonçalves, Fátima Martel

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