Targets of 3-Bromopyruvate, A New, Energy Depleting, Anticancer Agent

P.      Dell'Antone

Abstract

3-bromopyruvate (3-BrPA), a pyruvate analog recently proposed as a possible anticancer drug, was investigated in relation to its capacity to inhibit energy production in fractions obtained from normal cells (rat hepatocytes) and in isolated rat thymocytes. Findings were that main targets of the drug were glyceraldehyde 3-phosphate dehydrogenase, and not hexokinase as suggested for hepatoma cells, and succinate -driven ATP synthesis. Consistently with the above findings, in the normal cells studied (thymocytes) the drug elicited an important fall in ATP levels. The significance of the present findings in concern with a possible therapeutic usefulness of the drug is discussed.

Keywords: 3-Bromopyruvate, Warburg effect, tumor therapy, glycolysis, hexokinase, glyceraldehyde-3-phosphate dehydrogenase, oxidative phosphorylation, succinate dehydrogenase