Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment
Open accessAbstract
Tumor formation and growth depend on various biological metabolism processes that are distinctly different with normal tissues. Abnormal energy metabolism is one of the typical characteristics of tumors. It has been proven that most tumor cells highly rely on aerobic glycolysis to obtain energy rather than mitochondrial oxidative phosphorylation (OXPHOS) even in the presence of oxygen, a phenomenon called “Warburg effect”. Thus, inhibition of aerobic glycolysis becomes an attractive strategy to specifically kill tumor cells, while normal cells remain unaffected. In recent years, a small molecule alkylating agent, 3-bromopyruvate (3-BrPA), being an effective glycolytic inhibitor, has shown great potential as a promising antitumor drug. Not only it targets glycolysis process, but also inhibits mitochondrial OXPHOS in tumor cells. Excellent antitumor effects of 3-BrPA were observed in cultured cells and tumor-bearing animal models. In this review, we described the energy metabolic pathways of tumor cells, mechanism of action and cellular targets of 3-BrPA, antitumor effects, and the underlying mechanism of 3-BrPA alone or in combination with other antitumor drugs (e.g., cisplatin, doxorubicin, daunorubicin, 5-fluorouracil, etc.) in vitro and in vivo. In addition, few human case studies of 3-BrPA were also involved. Finally, the novel chemotherapeutic strategies of 3-BrPA, including wafer, liposomal nanoparticle, aerosol, and conjugate formulations, were also discussed for future clinical application.
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- Authors
- Fan, T., Sun, G., Sun, X., Zhao, L., Zhong, R., & Peng, Y.
- Affiliations
- Beijing University of Technology (CN)
- Corresponding author
- Sun, Guohui
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2019-03-06
- Volume
- 11
- Issue
- 3
- Pages
- 317
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC6468516
- OpenAlex
- W2920277785
- Cited by
- 171
- References
- 137
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 17 · 2023: 32 · 2022: 29 · 2021: 32 · 2020: 22 · 2019: 10
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Beijing Natural Science Foundation (7184192, 7162015)
- Natural Science Foundation of China (21778011)
- China Postdoctoral Science Foundation funded project (No. 2017M620567)
- Beijing Postdoctoral Research Foundation (No. 2018-ZZ-022)
- Chaoyang District Postdoctoral Research Foundation (No. 2018ZZ-01-25)
- the Great Wall scholars program of Beijing Municipal Education Commission (No. CIT&TCD20180308)
- Education Commission Science and Technology Project of Beijing Municipality (No. PXM2015_014204_500175)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- 3-bromopyruvate, aerobic glycolysis, Warburg effect, tumor energy metabolism, mitochondrial oxidative phosphorylation, glycolysis inhibitors, anticancer agents, combination chemotherapy, drug formulation, liposomal nanoparticles, aerosol drug delivery, alkylating agents
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