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. 2014 Apr 9;19(2):201–214. doi: 10.2478/s11658-014-0189-1

Transport of 3-bromopyruvate across the human erythrocyte membrane

Izabela Sadowska-Bartosz 1,5,✉, Mirosław Soszyński 2, Stanisław Ułaszewski 3, Young Ko 4, Grzegorz Bartosz 1,2
PMCID: PMC6275894  PMID: 24715475

Abstract

3-Bromopyruvic acid (3-BP) is a promising anticancer compound because it is a strong inhibitor of glycolytic enzymes, especially glyceraldehyde 3-phosphate dehydrogenase. The Warburg effect means that malignant cells are much more dependent on glycolysis than normal cells. Potential complications of anticancer therapy with 3-BP are side effects due to its interaction with normal cells, especially erythrocytes. Transport into cells is critical for 3-BP to have intracellular effects. The aim of our study was the kinetic characterization of 3-BP transport into human erythrocytes. 3-BP uptake by erythrocytes was linear within the first 3 min and pH-dependent. The transport rate decreased with increasing pH in the range of 6.0–8.0. The Km and Vm values for 3-BP transport were 0.89 mM and 0.94 mmol/(l cells x min), respectively. The transport was inhibited competitively by pyruvate and significantly inhibited by DIDS, SITS, and 1-cyano-4-hydroxycinnamic acid. Flavonoids also inhibited 3-BP transport: the most potent inhibition was found for luteolin and quercetin.

Keywords: 3-Bromopyruvic acid, Erythrocytes, Polyphenols, Flavonoids, Transport, Monocarboxylate transporter, 1-Cyano-4-hydroxycinnamic acid, Luteolin, Quercetin

Full Text

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Abbreviations used

3-BP

3-bromopyruvate

CHC

1-cyano-4-hydroxycinnamic acid

DIDS

4,4′-diisothiocyanostilbene-2,2′-disulphonate

MCT

monocarboxylate transporter

SITS

4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid

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