Dataset Information

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells.

ABSTRACT: Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances.

SUBMITTER: Picard LK

PROVIDER: S-EPMC9655024 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells.

Picard Lea Katharina LK Littwitz-Salomon Elisabeth E Waldmann Herbert H Watzl Carsten C

Cells 20221103 21

Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits ...[more]

PMID: 36359883

Similar Datasets

Project description:Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis. To better understand the molecular mechanisms of RUNX2 gene action in ovarian cancer cells, we employed the Agilent Whole Human Genome microarrays, containing ~ 44,000 genes to identify global gene expression changes upon RUNX2 suppression in SKOV3 cells. We compared the gene expression of the previously selected clone shRNA- RUNX2-knockdown clone 3 (cl3) against the corresponding control clone. The microarray experiments were performed in duplicates, as two hybridizations were carried out for the RUNX2-suppressing cell clone against the corresponding control, using a fluorescent dye reversal (dye-swap) technique.

Project description:BackgroundBaeckea frutescens (B. frutescens) of the family Myrtaceae is a plant that has been used in traditional medicine. It is known to have antibacterial, antipyretic and cytoprotective properties. The objective of this study is to explore the mechanism of B. frutescens leaves extracts in eliminating breast cancer cells.MethodB. frutescens leaves extracts were prepared using Soxhlet apparatus with solvents of different polarity. The selective cytotoxicity of these extracts at various concentrations (20 to 160 μg/ml) were tested using cell viability assay after 24, 48 and 72 h of treatment. The IC50 value in human breast cancer (MCF-7 and MDA-MB-231) and mammary breast (MCF10A) cell lines were determined. Apoptotic study using AO/PI double staining was performed using fluorescent microscope. The glucose uptake was measured using 2-NBDG, a fluorescent glucose analogue. The phytochemical screening was performed for alkaloids, flavonoids, tannins, triterpenoids, and phenols.ResultsB. frutescens leaves extracts showed IC50 value ranging from 10 -127μg/ml in MCF-7 cells after 72 h of treatment. Hexane extract had the lowest IC50 value (10μg/ml), indicating its potent selective cytotoxic activity. Morphology of MCF-7 cells after treatment with B. frutescens extracts exhibited evidence of apoptosis that included membrane blebbing and chromatin condensation. In the glucose uptake assay, B. frutescens extracts suppressed glucose uptake in cancer cells as early as 24 h upon treatment. The inhibition was significantly lower compared to the positive control WZB117 at their respective IC50 value after 72 h incubation. It was also shown that the glucose inhibition is selective towards cancer cells compared to normal cells. The phytochemical analysis of the extract using hexane as the solvent in particular gave similar quantities of tannin, triterpenoids, flavonoid and phenols. Presumably, these metabolites have a synergistic effect in the in vitro testing, producing the potent IC50 value and subsequently cell death.ConclusionThis study reports the potent selective cytotoxic effect of B. frutescens leaves hexane extract against MCF-7 cancer cells. B. frutescens extracts selectively suppressed cancer cells glucose uptake and subsequently induced cancer cell death. These findings suggest a new role of B. frutescens in cancer cell metabolism.

Dataset Information

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells.

Publications

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets