Antitumor and chemosensitizing action of 3-bromopyruvate: Implication of deregulated metabolism

Yadav, Saveg; Pandey, Shrish Kumar; Kumar, Ajay; Kujur, Praveen Kumar; Singh, Rana P.; Singh, Sukh Mahendra

doi:10.1016/j.cbi.2017.04.015

Cited by 32 publications

(41 citation statements)

References 75 publications

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“…Previous studies revealed that cytochrome c release was involved in 3-BrPA-induced cell apoptosis [42], but no release of cytochrome c was found in the above study [58]. However, the following studies further showed 3-BrPA treatment resulted in an increase of cytochrome c release [59,60], along with an elevated expression of active proapoptotic caspase-3 and a decrease of antiapoptotic Bcl-2 and Mcl-1 [59]. Several recent studies indicated that 3-BrPA also inhibited the expression of HK-II at mRNA and protein levels [59,61].…”

Section: Properties Mechanism Of Action and Cellular Targets Of mentioning

confidence: 81%

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Fan

Sun

et al. 2019

Cancers

127

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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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Section: Properties Mechanism Of Action and Cellular Targets Of mentioning

confidence: 81%

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Fan

Sun

et al. 2019

Cancers

127

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“…Glycolytic inhibitors, such as 2-deoxyglucose (2DOG) and 3-bromopyruvate (3-BP), can be used as adjuvant agents to sensitize tumors. Unlike 2DOG, 3-BP acts in many targets and inhibits HK, GAPDH, and MCT activities, thus leading to decreased aerobic glycolysis ( 155 ). Furthermore, inhibition of PFK1 activity, a rate-limiting step of glycolysis, is also an interesting strategy in cancer therapy.…”

Section: Targeting Metabolism In Thyroid Cancermentioning

confidence: 99%

Metabolic Reprogramming in Thyroid Carcinoma

2018

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Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

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“…B-cell lymphoma 2, Mcl-1 and caspase-3 resulting in increased cytochrome c release. 3BP seems to be promising in treating thymic lymphoma [6].…”

Section: Bp Is Promising In Treating Lymphomamentioning

confidence: 99%

3-bromopyruvate as a Promising Treatment for Hematological Cancer

Ayat¹

2018

JCRT

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Many biological differences exist between cancer cells and normal cells that can act as potential targets in targeted cancer therapy. Hematological cancers e.g. lymphoma, leukemia and myeloma exhibit drug-resistance that ultimately results in deteriorated patients' conditions and high mortality rates. Resistance of hematological malignancy to conventional chemotherapy is attributed in part to upregulation of glucose oxidation (glycolysis) genes evidenced by gaining a promising chemosensitization effect upon adding a glycolysis inhibitor to chemotherapeutics. The promising anticancer agent 3-bromopyruvate (3BP) is a structural analog of both pyruvate and lactate. 3BP was reported to antagonize the Warburg effect (malignant phenotype where cancer cells utilize cytoplasmic glucose oxidation to produce ATP and lactate even in the presence of oxygen without making benefit of the generous ATP provision from glucose oxidation via mitochondrial pathways). Warburg effect deprives cancer cells from the high energetic yield achieved through utilizing mitochondrial pathways. 3BP is a promising antiglycolytic agent that targets major glycolysis enzymes (hexokinase II and glyceraldehyde-3-phosphate dehydrogenase. In this article, 3BP promising anticancer effects in treating lymphoma, leukemia and myeloma are discussed in addition to the mode of inhibition of Warburg effect using 3BP. In conclusion, 3BP is a promising anticancer drug (that will be more powerful upon proper pharmaceutical formulations) for treating hematological malignancies. 3BP is advisable to be included in treatment protocols in hematological cancers as a chemosensitizer or as a sole anticancer agent.

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Antitumor and chemosensitizing action of 3-bromopyruvate: Implication of deregulated metabolism

Cited by 32 publications

References 75 publications

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Tumor Energy Metabolism and Potential of 3-Bromopyruvate as an Inhibitor of Aerobic Glycolysis: Implications in Tumor Treatment

Metabolic Reprogramming in Thyroid Carcinoma

3-bromopyruvate as a Promising Treatment for Hematological Cancer

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