Anticancer agent 3-bromopyruvic acid forms a conjugate with glutathione

Background 3-bromopyruvic acid (3-bp),a glycolytic inhibitor and a promising anticancer compound,induces oxidative stress and depletes cells of glutathione (gsh). the causes of gsh loss remain unclear. the aim of this study was to ascertain whether 3-bp forms a conjugate with glutathione. methods gsh was incubated with various amounts of 3-bp and the extent of reaction was titrated with 1h nmr and 1h-1h nmr. the reaction outcome was identified by ms/ms. intracellular formation of the conjugate was assessed in cells treated with 3-bp and 3-bp(13c) and analyzed using the targeted lc-ms/ms method in negative ionization mrm mode. results 3-bp was found to react with gsh in a 1:1 ratio forming an s-conjugate. the same conjugate was formed intracellularly in erythrocytes and mcf-7 cells. conclusions 3-bp reacts with gsh in the absence of cells and intracellularly. this reaction appears to be the main cause of gsh loss in 3-bp treated cells. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.