Bile salts and proinflammatory cytokines inhibit MCT1-mediated cellular uptake of butyrate and interfere with its antiproliferative properties

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Couto, MR (Author) Other; Andrade, N (Author) Other; Magro, F (Author) Other; Martel, F (Author) FMUP

Journal

Title: Experimental Cell Research

Vol. 429

ISSN: 0014-4827

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: P-00Y-HTE

DOI: 10.1016/j.yexcr.2023.113670

Abstract (EN): Butyrate (BT) is important in the prevention and inhibition of colorectal cancer (CRC). Inflammatory bowel disease, a risk factor for CRC, is associated with higher levels of proinflammatory cytokines and bile acids. The aim of this work was to investigate the interaction of these compounds in inhibiting BT uptake by Caco-2 cells, as a mechanism contributing to the link between IBD and CRC.TNF-a, IFN-?, chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) markedly reduce 14C-BT uptake. All these compounds appear to inhibit MCT1-mediated BT cellular uptake at a posttranscriptional level, and, because their effect is not additive, they are most probably inhibiting MCT1 by a similar mechanism. Correspondingly, the antiproliferative effect of BT (MCT1-dependent) and of the proinflammatory cytokines and CDCA were not additive.In contrast, the cytotoxic effect of BT (MCT1-independent) and of the proinflammatory cytokines and CDCA were additive. In conclusion, proinflammatory cytokines (TNF-a and IFN-?) and bile acids (DCA and CDCA) inhibit MCT1mediated BT cellular uptake. These proinflammatory cytokines and CDCA were found to interfere with the antiproliferative effect of BT, mediated by an inhibitory effect upon MCT1-mediated cellular uptake of BT.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9