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.
Keywords: Alkylating agent, glycolysis, 3-bromopyruvate, anti-metabolite, GAPDH
Current Pharmaceutical Biotechnology
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.
Export Options
About this article
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
DOI https://dx.doi.org/10.2174/138920110791591427 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Cell Cycle and Cancer: The G1 Restriction Point and the G1 / S Transition
Current Genomics Lipid Nucleoside Conjugates for the Treatment of Cancer
Current Pharmaceutical Design Synergistic Antiproliferative and Antiangiogenic Effects of EGFR and mTOR Inhibitors
Current Pharmaceutical Design The Promise of miRNA Replacement Therapy for Hepatocellular Carcinoma
Current Gene Therapy Approaches for Imaging the Diabetic Pancreas: First Results
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Herpesvirus Saimiri Terminal Membrane Proteins Modulate HIV-1 Replication By Altering Nef and Tat Functions
Current HIV Research Screening for Infectious Diseases During Pregnancy: Which Test and Which Situation
Current Women`s Health Reviews <i>Nigella sativa</i> – A Functional Spice From A Pharaoh’s Tomb to Modern Healthcare
The Natural Products Journal Small Molecules ATP-Competitive Inhibitors of FLT3: A Chemical Overview
Current Medicinal Chemistry Tumor Necrosis Factor-α, a Regulator and Therapeutic Agent on Breast Cancer
Current Pharmaceutical Biotechnology Immunotherapeutic Approaches in Pancreatic Adenocarcinoma: Current Status and Future Perspectives
Current Molecular Pharmacology Murine Models of Vpr-Mediated Pathogenesis
Current HIV Research Iron Oxide Nanoparticle Platform for Biomedical Applications
Current Medicinal Chemistry Antiviral Drugs in the Prophylaxis of HBV Infection
Current Medicinal Chemistry Future Targets in Endothelial Biology: Endothelial Cell to Mesenchymal Transition
Current Drug Targets Mechanisms of Anorexia Cancer Cachexia Syndrome and Potential Benefits of Traditional Medicine and Natural Herbs
Current Pharmaceutical Biotechnology The Pro-Survival Function of Akt Kinase can be Overridden or Altered to Contribute to Induction of Apoptosis
Current Cancer Drug Targets Nitric Oxide-Releasing Biomaterials for Biomedical Applications
Current Medicinal Chemistry Nanosized Tamoxifen-Porphyrin-Glucose [TPG] Conjugate: Novel Selective Anti-breast-cancer Agent, Synthesis and In Vitro Evaluations
Medicinal Chemistry p53-Induced Apoptosis and Inhibitors of p53
Current Medicinal Chemistry