Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate.

Journal of Bioenergetics and Biomembranes
Odília QueirósMargarida Casal

Abstract

Most malignant tumors exhibit the Warburg effect, which consists in increased glycolysis rates with production of lactate, even in the presence of oxygen. Monocarboxylate transporters (MCTs), maintain these glycolytic rates, by mediating the influx and/or efflux of lactate and are overexpressed in several cancer cell types. The lactate and pyruvate analogue 3-bromopyruvate (3-BP) is an inhibitor of the energy metabolism, which has been proposed as a specific antitumor agent. In the present study, we aimed at determining the effect of 3-BP in breast cancer cells and evaluated the putative role of MCTs on this effect. Our results showed that the three breast cancer cell lines used presented different sensitivities to 3-BP: ZR-75-1 ER (+)>MCF-7 ER (+)>SK-BR-3 ER (-). We also demonstrated that 3-BP reduced lactate production, induced cell morphological alterations and increased apoptosis. The effect of 3-BP appears to be cytotoxic rather than cytostatic, as a continued decrease in cell viability was observed after removal of 3-BP. We showed that pre-incubation with butyrate enhanced significantly 3-BP cytotoxicity, especially in the most resistant breast cancer cell line, SK-BR-3. We observed that butyrate treatment induced localiz...Continue Reading

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Citations

Jul 3, 2013·Journal of Bioenergetics and Biomembranes·Diana Tavares-ValenteOdília Queirós
Jun 15, 2014·Mitochondrion·M Adeva-AndanyJ Rodríguez-Seijas
Dec 31, 2015·Journal of Bioenergetics and Biomembranes·Ewa KwiatkowskaIzabela Sadowska-Bartosz
May 9, 2014·Journal of Animal Physiology and Animal Nutrition·F DenglerG Gäbel
Feb 3, 2015·The Biochemical Journal·João Azevedo-SilvaMargarida Casal
May 21, 2014·The International Journal of Biochemistry & Cell Biology·Antonio Galina
Apr 23, 2016·Cell Cycle·Céline PinheiroVinicius L Vazquez
Jul 28, 2016·Journal of Bioenergetics and Biomembranes·J Azevedo-SilvaM Casal
Nov 5, 2016·Biochimica Et Biophysica Acta·Xianbin SuJimmy S H Tsang
Nov 21, 2015·Oncotarget·Céline PinheiroMaria C N Zerbini
Apr 18, 2019·FEMS Yeast Research·Katarzyna NiedźwieckaStanisław Ułaszewski
Feb 3, 2021·Advances in Nutrition·Philippe IcardMarco Alifano
Jan 10, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Cinzia BragatoMarina Mora
Jul 3, 2021·International Journal of Molecular Sciences·Magdalena CalStanisław Ułaszewski

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