Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection

Dey, Sananda; Murmu, Nensina; Mondal, Tanushree; Saha, Ishita; Chatterjee, Soumendranath; Manna, Rahul; Haldar, Subhash; Dash, Sandeep Kumar; Sarkar, Tapasree Roy; Giri, Biplab

doi:10.1016/j.biopha.2022.113801

Cited by 18 publications

(15 citation statements)

References 202 publications

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“…Second, 2-DG May influence migraine-related behaviors through a variety of pathways. 2-DG can inhibit PI3K/Akt/mTOR and up-regulate AMPK pathway to reduce inflammation and oxidative stress ( 56 , 57 ). This study only discussed the mechanism of glycolysis related to inflammation, while the possible effect of 2-DG on migraine through oxidative stress and PI3K/Akt pathway remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine

Qiu

Zhou

et al. 2023

Front. Neurol.

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BackgroundTargeting metabolic pathways has emerged as a new migraine treatment strategy as researchers realize the critical role metabolism plays in migraine. Activated inflammatory cells undergo metabolic reprogramming and rely on glycolysis to function. The objective of this study was to investigate the glycolysis changes in the experimental model of migraine and the effect of glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) in the pathophysiology of migraine.MethodsWe used a rat model of migraine that triggered migraine attacks by applying inflammatory soup (IS) to the dura and examined changes in glycolysis. 2-DG was used to inhibit glycolysis, and the effects of 2-DG on mechanical ectopic pain, microglial cell activation, calcitonin gene-related peptides (CGRP), c-Fos, and inflammatory factors induced by inflammatory soup were observed. LPS stimulated BV2 cells to establish a model in vitro to observe the effects of 2-DG on brain-derived neurotrophic factor (BDNF) after microglia activation.ResultsIn the experimental model of migraine, key enzymes involved in glycolysis such as phosphofructokinase platelet (PFKP), hexokinase (HK2), hypoxia inducible factor-1α (HIF-1α), lactate dehydrogenase (LDH) and pyruvate kinase (PKM2) were expressed in the medullary dorsal horn. While the expression of electronic respiratory transport chain complex IV (COXIV) decreased. There were no significant changes in glucose 6-phosphate dehydrogenase (G6PD), a key enzyme in the pentose phosphate pathway. The glycolysis inhibitor 2-DG alleviated migraine-like symptoms in an experimental model of migraine, reduced the release of proinflammatory cytokines caused by microglia activation, and decreased the expression of CGRP and c-Fos. Further experiments in vitro demonstrated that glycolysis inhibition can reduce the release of Iba-1/proBDNF/BDNF and inhibit the activation of microglia.ConclusionThe migraine rat model showed enhanced glycolysis. This study suggests that glycolytic inhibitor 2-DG is an effective strategy for alleviating migraine-like symptoms. Glycolysis inhibition may be a new target for migraine treatment.

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Section: Discussionmentioning

confidence: 99%

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine

Qiu

Zhou

et al. 2023

Front. Neurol.

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“…Te molecule 2-DG follows Lipinski's rule of fve and has several activities, kills hypoxic tumor cells, and lowers oxygen dependency in case of Covid-19 (Figure 2). A number of studies have described diferent biological activities [3], but it is not approved as a drug until May 2021 [15]. In May 2021, 2-DG was found an emergency use as an anti-Covid-19 drug allowing patients to recuperate more quickly by lowering the need for supplemental oxygen.…”

Section: Pharmaceutical Profile Of 2-dgmentioning

confidence: 99%

“…Recent reports suggest the usefulness of 2-deoxy-D-glucose in the inhibition of infammation [23], controlling respiratory infections, and treatment of human genital herpes [24]. 2-DG shows antiinfammatory activities through the regulation of antiinfammatory mediators and the polarization of macrophages [3]. During ocular infection with herpes simplex virus (HSV), stromal keratitis occurs due to infammatory reactions in the eye.…”

Section: Inhibition Of Infammationmentioning

confidence: 99%

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2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities

Singh¹,

Gupta

Kumar

et al. 2023

Advances in Pharmacological and Pharmaceutical Sciences

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The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present review, various pharmaceutical properties of 2-DG are discussed.

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“…Cancer cells require glycolysis to generate energy, so they have a higher demand for simple sugars like D-glucose. 19 As polar molecules cannot pass through the impermeable cell membrane, the glucose intake is regulated by specialized membrane transporters (GLUT and SGLT). 20 These transporters facilitate D-glucose penetration because they are overexpressed in different types of cancer cells.…”

Section: ■ Introductionmentioning

confidence: 99%

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Pragti,

Kundu,

Singh

et al. 2023

ACS Appl. Mater. Interfaces

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The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)–biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV–vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer–Emmett–Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.

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Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection

Cited by 18 publications

References 202 publications

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine

2-Deoxyglucose alleviates migraine-related behaviors by modulating microglial inflammatory factors in experimental model of migraine

2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities

Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

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