title: 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy.
abstract: The pyruvate analog, 3-bromopyruvate, is an alkylating agent and a potent inhibitor of glycolysis. This antiglycolytic property of 3-bromopyruvate has recently been exploited to target cancer cells, as most tumors depend on glycolysis for their energy requirements. The anticancer effect of 3-bromopyruvate is achieved by depleting intracellular energy (ATP) resulting in tumor cell death. In this review, we will discuss the principal mechanism of action and primary targets of 3-bromopyruvate, and report the impressive antitumor effects of 3-bromopyruvate in multiple animal tumor models. We describe that the primary mechanism of 3-bromopyruvate is via preferential alkylation of GAPDH and that 3-bromopyruvate mediated cell death is linked to generation of free radicals. Research in our laboratory also revealed that 3-bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Therefore, these and other studies reveal the tremendous potential of 3-bromopyruvate as an anticancer agent.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ganapathy-Kanniappan
authors.forename: M
authors.initials: M
authors.lastname: Vali
authors.forename: R
authors.initials: R
authors.lastname: Kunjithapatham
authors.forename: M
authors.initials: M
authors.lastname: Buijs
authors.forename: L H
authors.initials: LH
authors.lastname: Syed
authors.forename: P P
authors.initials: PP
authors.lastname: Rao
authors.forename: S
authors.initials: S
authors.lastname: Ota
authors.forename: B K
authors.initials: BK
authors.lastname: Kwak
authors.forename: R
authors.initials: R
authors.lastname: Loffroy
authors.forename: J F
authors.initials: JF
authors.lastname: Geschwind
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D011773:Pyruvates
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; C017092:bromopyruvate; D005947:Glucose