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Inhibition of butyrate uptake by the primary bile salt chenodeoxycholic acid in intestinal epithelial cells
Author(s) -
Gonçalves Pedro,
Catarino Telmo,
Gregório Inês,
Martel Fátima
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24172
Subject(s) - chenodeoxycholic acid , butyrate , bile acid , primary (astronomy) , chemistry , salt (chemistry) , medicine , biochemistry , physics , fermentation , astronomy
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. Finally, BT (5 mM) decreased IEC‐6 cell viability and increased IEC‐6 cell differentiation, and CDCA (100 µM) reduced this effect. In conclusion, CDCA is an effective inhibitor of 14 C‐BT uptake in tumoral and non‐tumoral intestinal epithelial cells, through inhibition of both H + ‐coupled MCT1‐ and SMCT1‐mediated transport. Given the role played by BT in the intestine, this mechanism may contribute to the procarcinogenic effect of CDCA at this level. J. Cell. Biochem. 113: 2937–2947, 2012. © 2012 Wiley Periodicals, Inc.