Transport of 3-bromopyruvate across the human erythrocyte membrane.
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.
Department of Biochemistry and Cell Biology, University of Rzeszów, Rzeszów, Poland, sadowska@univ.rzeszow.pl.
Izabela
I
Sadowska-Bartosz
Mirosław
M
Soszyński
Stanisław
S
Ułaszewski
Young
Y
Ko
Grzegorz
G
Bartosz
D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011773:Pyruvates / Q000378:metabolism*; D013696:Temperature
D005419:Flavonoids; D011773:Pyruvates; C017092:bromopyruvate