Protective and recuperative effects of 3-bromopyruvate on immunological, hepatic and renal homeostasis in a murine host bearing ascitic lymphoma: Implication of niche dependent differential roles of macrophages

Yadav, Saveg; Pandey, Shrish Kumar; Goel, Yugal; Kujur, Praveen Kumar; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana P.; Singh, Sukh Mahendra

doi:10.1016/j.biopha.2018.01.149

Cited by 13 publications

(8 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that two recent studies comprehensively described the effects of 3-BrPA on the homeostasis and tumor microenvironment (TME) of tumor-bearing animals, which would assist in optimizing therapeutic regimen of 3-BrPA in future clinical oncology [60,122]. In the first study, 3-BrPA exhibited protective and recuperative effects on the immunological, splenic, hepatic, and renal homeostasis in DL tumor-bearing mice, including reversion of tumor growth associated thymic atrophy and organomegaly (splenomegaly, hepatomegaly, and renomegaly), activation of tumor associated macrophages mediated by IFN-γ, increase of blood leukocytes (CD4+, CD8+ T lymphocytes, and NK cells) and IL-2 receptor expressing cells, alteration of serum cytokine balance, reduction of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) [122]. In another study carried out by the same research group, they further investigated the effect of 3-BrPA on tumor growth regulatory components of TME in vivo [60].…”

Section: Antitumor Effects Of 3-brpa and The Underlying Mechanismmentioning

confidence: 99%

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

Fan

Sun

et al. 2019

Cancers

117

View full text Add to dashboard Cite

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.

show abstract

Section: Antitumor Effects Of 3-brpa and The Underlying Mechanismmentioning

confidence: 99%

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

Fan

Sun

et al. 2019

Cancers

117

View full text Add to dashboard Cite

show abstract

“…TAMs harvested from tumor-bearing mice treated with 3-BP displayed enhanced tumoricidal activity and pro-inflammatory cytokine (IL-1, TNFα) production. However, TAM culture with 3-BP alone did not induce any changes in TAM cytotoxic function (Yadav et al, 2018) despite inhibiting the first step of glycolysis (Errea et al, 2016). Clearly, glycolytic drugs that are effective toward cancer cells might not necessarily be as effective toward TAMs.…”

Section: Targeting Warburg Metabolism In Myeloid Cellsmentioning

confidence: 96%

The Sweet Surrender: How Myeloid Cell Metabolic Plasticity Shapes the Tumor Microenvironment

Sieow

Gun

Wong

2018

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Immune cells are one of the most versatile cell types, as they can tailor their metabolic activity according to their required function. In response to diverse environmental cues, immune cells undergo metabolic reprogramming to support their differentiation, proliferation and pro-inflammatory effector functions. To meet a dramatic surge in energetic demand, immune cells rewire their metabolism to utilize aerobic glycolysis. This preferential use of glycolysis even under aerobic conditions is well established in tumor cells, and is known as the “Warburg effect.” Tumor cells avidly use glucose for aerobic glycolysis, thereby creating a nutrient-starved microenvironment, outcompeting T cells for glucose, and directly inhibiting T-cell anti-tumoral effector function. Given that both immune and tumor cells use similar modes of metabolism in the tumor stroma, it is imperative to identify a therapeutic window in which immune-cell and tumor-cell glycolysis can be specifically targeted. In this review, we focus on the Warburg metabolism as well as other metabolic pathways of myeloid cells, which comprise a notable niche in the tumor environment and promote the growth and metastasis of malignant tumors. We examine how differential immune-cell activation triggers metabolic fate, and detail how this forbidding microenvironment succeeds in shutting down the vigorous anti-tumoral response. Finally, we highlight emerging therapeutic concepts that aim to target immune-cell metabolism. Improving our understanding of immunometabolism and immune-cell commitment to specific metabolic fates will help identify alternative therapeutic approaches to battle this intractable disease.

show abstract

“…Given the fact that most anticancer drugs inflict cytotoxicity to normal cells, tissues, and organs in cancer patients (Cheok, 2012), safety concerns are of primary focus while designing and developing chemotherapeutic agents. It has been demonstrated that the antitumor action of 3-BP is accompanied by protective and recuperative effects on immunological, hepatic, and renal homeostasis, with normalization of liver and kidney functions, reduction of tumor growth-associated splenomegaly, restored thymic homeostasis, normalization of blood lymphocytes, and upregulated myelopoiesis (Yadav et al, 2018). Additionally, other studies showed that 3-BP was safe to various tissues (Kunjithapatham et al, 2013; Pan et al, 2016), displaying minimal hepatic and nephrotoxicity (Pan et al, 2016).…”

Section: -Bromopyruvate Is Capable Of Multifaceted Targeting Of Tumomentioning

confidence: 99%

“…Moreover, these limited clinical trials have shown minimal side effects, except minor concerns regarding burning sensation and phlebitis (El Sayed, 2018). Most preclinical and clinical trials report about its safety concerning hepatic functions (Ko et al, 2012; El Sayed et al, 2014; Pan et al, 2016; Yadav et al, 2018). The main recommendations for overcoming the limitations regarding the use of 3-BP include strict implementation of only formulated preparations in human applications (El Sayed, 2018; Fan et al, 2019b), use of GSH scavengers accompanying 3-BP administration because GSH can inactivate 3-BP (El Sayed, 2018), and strict monitoring of the dose regimens (El Sayed, 2018).…”

Section: Limitations and Prospectsmentioning

confidence: 99%

Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate

et al. 2019

Self Cite

View full text Add to dashboard Cite

Malignant cells possess a unique metabolic machinery to endure unobstructed cell survival. It comprises several levels of metabolic networking consisting of 1) upregulated expression of membrane-associated transporter proteins, facilitating unhindered uptake of substrates; 2) upregulated metabolic pathways for efficient substrate utilization; 3) pH and redox homeostasis, conducive for driving metabolism; 4) tumor metabolism-dependent reconstitution of tumor growth promoting the external environment; 5) upregulated expression of receptors and signaling mediators; and 6) distinctive genetic and regulatory makeup to generate and sustain rearranged metabolism. This feat is achieved by a “battery of molecular patrons,” which acts in a highly cohesive and mutually coordinated manner to bestow immortality to neoplastic cells. Consequently, it is necessary to develop a multitargeted therapeutic approach to achieve a formidable inhibition of the diverse arrays of tumor metabolism. Among the emerging agents capable of such multifaceted targeting of tumor metabolism, an alkylating agent designated as 3-bromopyruvate (3-BP) has gained immense research focus because of its broad spectrum and specific antineoplastic action. Inhibitory effects of 3-BP are imparted on a variety of metabolic target molecules, including transporters, metabolic enzymes, and several other crucial stakeholders of tumor metabolism. Moreover, 3-BP ushers a reconstitution of the tumor microenvironment, a reversal of tumor acidosis, and recuperative action on vital organs and systems of the tumor-bearing host. Studies have been conducted to identify targets of 3-BP and its derivatives and characterization of target binding for further optimization. This review presents a brief and comprehensive discussion about the current state of knowledge concerning various aspects of tumor metabolism and explores the prospects of 3-BP as a safe and effective antineoplastic agent.

show abstract

Protective and recuperative effects of 3-bromopyruvate on immunological, hepatic and renal homeostasis in a murine host bearing ascitic lymphoma: Implication of niche dependent differential roles of macrophages

Cited by 13 publications

References 64 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

The Sweet Surrender: How Myeloid Cell Metabolic Plasticity Shapes the Tumor Microenvironment

Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate

Contact Info

Product

Resources

About