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Licensed Unlicensed Requires Authentication Published by De Gruyter February 14, 2019

MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions

  • Joana Pereira-Vieira , João Azevedo-Silva ORCID logo , Ana Preto , Margarida Casal and Odília Queirós EMAIL logo
From the journal Biological Chemistry

Abstract

Monocarboxylate transporters (MCTs) inhibition leads to disruption in glycolysis, induces cell death and decreases cell invasion, revealing the importance of MCT activity in intracellular pH homeostasis and tumor aggressiveness. 3-Bromopyruvate (3BP) is an anti-tumor agent, whose uptake occurs via MCTs. It was the aim of this work to unravel the importance of extracellular conditions on the regulation of MCTs and in 3BP activity. HCT-15 was found to be the most sensitive cell line, and also the one that presented the highest basal expression of both MCT1 and of its chaperone CD147. Glucose starvation and hypoxia induced an increased resistance to 3BP in HCT-15 cells, in contrast to what happens with an extracellular acidic pH, where no alterations in 3BP cytotoxicity was observed. However, no association with MCT1, MCT4 and CD147 expression was observed, except for glucose starvation, where a decrease in CD147 (but not of MCT1 and MCT4) was detected. These results show that 3BP cytotoxicity might include other factors beyond MCTs. Nevertheless, treatment with short-chain fatty acids (SCFAs) increased the expression of MCT4 and CD147 as well as the sensitivity of HCT-15 cells to 3BP. The overall results suggest that MCTs influence the 3BP effect, although they are not the only players in its mechanism of action.

Acknowledgments

To Andre Goffeau, who passed away on April 2nd, 2018, in memoriam. He was always a very active collaborator in this project and a great contributor to the results herein presented. He had a dream of finding a cure for cancer and had a great hope in the use of 3BP. This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P., by the Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by an internal CESPU project 02-GBMC-CICS-2011 MetabRes_CESPU_2017.

  1. Conflict of interest statement: The authors declare no conflict of interest.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2018-0411).


Received: 2018-10-26
Accepted: 2019-01-16
Published Online: 2019-02-14
Published in Print: 2019-06-26

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