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

Here, we introduce sublines of the EGFR-mutant non-small cell lung cancer (NSCLC) cell lines HCC827 and HCC4006 adapted to the EGFR kinase inhibitors gefitinib (HCC827rGEFI2µM, HCC4006rGEFI1µM), erlotinib (HCC827rERLO2µM, HCC4006rERLO1µM), and afatinib (HCC827rAFA50nM, HCC4006rAFA100nM). All sublines displayed resistance to gefitinib, erlotinib, afatinib, and the third-generation EGFR kinase inhibitor osimertinib that overcomes T790M-mediated resistance. HCC4006rERLO1µMdisplayed a spindle-like morphology in agreement with previous findings that had detected epithelial-mesenchymal-transition (EMT) in its precursor cell line HCC4006rERLO0.5µM. EMT had also been reported for the HCC4006rGEFI1µMprecursor cell line HCC4006rGEFI0.5µMand for HCC4006rAFA100nM, but the morphologies of HCC4006rGEFI1µMor HCC4006rAFA100nMdid not support this, suggesting plasticity in EMT regulation during the drug adaptation process and in established resistant cell lines. Accordingly, HCC4006rERLO1µMdisplayed resistance to MEK and AKT inhibitors in contrast to its precursor HCC4006rERLO0.5µM. We also detected metabolic plasticity, i.e., a temporary Warburg metabolism, in HCC4006 and HCC827rGEFI2µM. Response profiles to cytotoxic anti-cancer drugs, kinase inhibitors, and HDAC inhibitors resulted in complex patterns that were specific for each individual subline without obvious overlaps, indicating individual resistance phenotypes. All resistant sublines remained sensitive or displayed collateral sensitivity to at least one of the investigated drugs. In conclusion, the comparison of EGFR kinase-resistant NSCLC sublines with their precursor cell lines that had been previously characterised at a lower resistance level and metabolic investigations indicated phenotypic plasticity during the resistance formation process and in established cell lines. This plasticity may contribute to the well-known variability in cell line phenotypes observed between different laboratories and in intra-laboratory experiments.

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2-Deoxyglucose Promotes Anti-Inflammatory Polarization of Peritoneal Macrophages in Mice With Lewis Lung Carcinoma

Stepanov,

Yakshibaeva,

Kolesnik

et al. 2024

Oncology

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Summary. Aim: to investigate the effect of 2-deoxyglucose at a wide range of concentrations on the polarization of peritoneal macrophages of intact mice and mice with Lewis lung carcinoma. Object and methods: peritoneal macrophages obtained from intact female C57BL/6 mice and Lewis lung carcinoma-bearing mice. isolation of peritoneal macrophages, determination of nitric oxide production and arginase activity. Results: 2-deoxyglucose does not affect nitric oxide production and arginase activity of peritoneal macrophages of intact mice. 2-deoxyglucose at a concentration of 10 mM significantly (by 17%, p<0.05) increases arginase activity in peritoneal macrophages of mice with Lewis lung carcinoma. Conclusions: It was revealed that peritoneal macrophages in mice with Lewis lung carcinoma have a pro-inflammatory M1 phenotype. The addition of 2-deoxyglucose at a concentration of 10 mM to the incubation medium of peritoneal macrophages obtained from mice with Lewis lung carcinoma promotes a switch in macrophage polarization to the M2 phenotype.

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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

Cited by 7 publications

References 142 publications

Molecular analysis of dUTPase of Helicobacter pylori for identification of novel inhibitors using in silico studies

Molecular analysis of dUTPase of Helicobacter pylori for identification of novel inhibitors using in silico studies

Phenotypic plasticity in a novel set of EGFR tyrosine kinase inhibitor-adapted non-small cell lung cancer cell lines

2-Deoxyglucose Promotes Anti-Inflammatory Polarization of Peritoneal Macrophages in Mice With Lewis Lung Carcinoma

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