3-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy

Title: 3-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy

Volume: 11 Issue: 5

Author(s): S. Ganapathy-Kanniappan, M. Vali, R. Kunjithapatham, M. Buijs, L.H. Syed, P.P. Rao, S. Ota, B.K. Kwak, R. Loffroy and J.F. Geschwind

Affiliation:

Keywords: Alkylating agent, glycolysis, 3-bromopyruvate, anti-metabolite, GAPDH

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.

Cite this article as:

Ganapathy-Kanniappan S., Vali M., Kunjithapatham R., Buijs M., Syed L.H., Rao P.P., Ota S., Kwak B.K., Loffroy R. and Geschwind J.F., 3-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy, Current Pharmaceutical Biotechnology 2010; 11 (5) . https://dx.doi.org/10.2174/138920110791591427