Mitochondria: 3-bromopyruvate vs. mitochondria? A small molecule that attacks tumors by targeting their bioenergetic diversity.
Enhanced glycolysis, the classic bioenergetic phenotype of cancer cells was described by Otto Warburg approximately 90 years ago. However, the Warburg hypothesis does not necessarily imply mitochondrial dysfunction. The alkyl-halogen, 3-bromopyruvate (3BP), would not be expected to have selective targets for cancer therapy due to its high potential reactivity toward many SH side groups. Contrary to predictions, 3BP interferes with glycolysis and oxidative phosphorylation in cancer cells without side effects in normal tissues. The mitochondrial hexokinase II has been claimed as the main target. This "Organelle in focus" article presents a historical view of the use of 3BP in biochemistry and its effects on ATP-producing pathways of cancer cells. I will discuss how the alkylated enzymes contribute to the cooperative collapse of mitochondria and apoptosis. Perspectives for targeting 3BP to bioenergetics enzymes for cancer treatment will be considered.
Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Brazil. Electronic address: galina@bioqmed.ufrj.br.
Antonio
A
Galina
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000037:antagonists & inhibitors*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C017092:bromopyruvate; D006593:Hexokinase
3-Bromopyruvate; Alkylation; Glycolytic inhibitor; Mitochondrial respiration inhibitor; Tumor cell metabolism