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Transport of 3-bromopyruvate across the human erythrocyte membrane

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.

Abbreviations

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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Correspondence to Izabela Sadowska-Bartosz.

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Sadowska-Bartosz, I., Soszyński, M., Ułaszewski, S. et al. Transport of 3-bromopyruvate across the human erythrocyte membrane. Cell Mol Biol Lett 19, 201–214 (2014). https://doi.org/10.2478/s11658-014-0189-1

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Keywords

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