Transport of 3-bromopyruvate across the human erythrocyte membrane

Cell Mol Biol Lett. 2014 Jun;19(2):201-14. doi: 10.2478/s11658-014-0189-1. Epub 2014 Apr 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Transport / drug effects
  • Erythrocyte Membrane / metabolism*
  • Erythrocytes / cytology
  • Erythrocytes / metabolism*
  • Female
  • Flavonoids / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Pyruvates / metabolism*
  • Temperature

Substances

  • Flavonoids
  • Pyruvates
  • bromopyruvate