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.
Original language | English (US) |
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Pages (from-to) | 510-517 |
Number of pages | 8 |
Journal | Current Pharmaceutical Biotechnology |
Volume | 11 |
Issue number | 5 |
DOIs | |
State | Published - Sep 20 2010 |
Keywords
- 3-Bromopyruvate
- Alkylating agent
- Anti-metabolite
- GAPDH
- Glycolysis
ASJC Scopus subject areas
- Biotechnology
- Pharmaceutical Science