Early changes in glucose and phospholipid metabolism following apoptosis induction by IFN‐γ/TNF‐α in HT‐29 cells

Lutz, Norbert W.; Tome, Margaret E.; Cozzone, Patrick J.

doi:10.1016/s0014-5793(03)00489-7

Cited by 29 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many studies demonstrate the link between glycolysis and VEGF activation. Though hypoxia is a definite VEGF trigger [29], normoxic cells or cancer cells exposed to inflammatory stimuli, such as interferon, tumour necrosis factor-a and interleukin, may manifest phenotypic changes like those observed in hypoxic cells [30]. These inflammatory stimuli also induce VEGF secretion in lung cancer with MPE [9,31].…”

Section: Discussionmentioning

confidence: 99%

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

et al. 2010

View full text Add to dashboard Cite

Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation.Three tissue sample cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative realtime PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy.20 up-or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early-to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell.Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Aberrant choline phospholipid metabolism has also been demonstrated in inflammation-related pathologies (12,13) and neurological disorders, such as multiple sclerosis (14), Alzheimer's disease (15), and Gaucher's disease (16). Apoptosis has been linked to altered choline phospholipid metabolite concentrations as well (17). As shown in the schematic in Fig.…”

Section: Introductionmentioning

confidence: 98%

Molecular Causes of the Aberrant Choline Phospholipid Metabolism in Breast Cancer

Glunde

Jie²,

Bhujwalla³

2004

Cancer Research

333

332

View full text Add to dashboard Cite

Proton magnetic resonance spectroscopy ( 1 H MRS) consistently detects significant differences in choline phospholipid metabolites of malignant versus benign breast lesions. It is critically important to understand the molecular causes underlying these metabolic differences, because this may identify novel targets for attack in cancer cells. In this study, differences in choline membrane metabolism were characterized in breast cancer cells and normal human mammary epithelial cells (HMECs) labeled with [1,2-13 C]choline, using 1 H and 13 C magnetic resonance spectroscopy. Metabolic fluxes between membrane and water-soluble pool of choline-containing metabolites were assessed by exposing cells to [1,2-13 C]choline for long and short periods of time to distinguish between catabolic and anabolic pathways in choline metabolism. Gene expression analysis using microarrays was performed to understand the molecular mechanisms underlying these changes. Breast cancer cells exhibited increased phosphocholine (PC; P < 0.001), total choline-containing metabolites (P < 0.01), and significantly decreased glycerophosphocholine (P < 0.05) compared with normal HMECs. Decreased 13 C-enrichment was detected in choline (P < 0.001) and phosphocholine (P < 0.05, P < 0.001) of breast cancer cells compared with HMECs, indicating a higher metabolic flux from membrane phosphatidylcholine to choline and phosphocholine in breast cancer cells. Choline kinase and phospholipase C were significantly overexpressed, and lysophospholipase 1, phospholipase A2, and phospholipase D were significantly underexpressed, in breast cancer cells compared with HMECs. The magnetic resonance spectroscopy data indicated that elevated phosphocholine in breast cancer cells was primarily attributable to increased choline kinase activity and increased catabolism mediated by increased phospholipase C activity. These observations were consistent with the overexpression of choline kinase and phospholipase C detected in the microarray analyses.

show abstract

“…Lactate production was also increased, suggesting an increased rate of glycolysis. Several 1 H nuclear magnetic resonance studies have reported increased lactate production by tumors both in vivo and in vitro (23)(24)(25) during response to treatment. Santini et al (23) showed increased lactate levels by osteosarcoma cells during the first 24 h after treatment with radiation.…”

Section: Discussionmentioning

confidence: 99%

“…The posttherapy increase in lactate production occurred in cells grown both as monolayers and as 3-dimensional microspheroids. Lutz et al (24) showed that treatment of human colon adenocarcinoma cells (HT-29) with a combination of g-interferon and tumor necrosis factor a, which was shown to induce apoptosis, caused a time-dependent increase in lactate production between 4 and 15 h after the addition of treatment. Increased lactate levels have also been detected after treatment of HeLa tumor cells with radiation (25).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Breast Tumor Cells In Vitro with the Mitochondrial Membrane Potential Dissipater Valinomycin Increases 18F-FDG Incorporation

Smith

Blaylock²

2007

Journal of Nuclear Medicine

View full text Add to dashboard Cite

Mitochondrial membrane potential is essential for adenosine triphosphate (ATP) synthesis by oxidative phosphorylation, and its abolition is an early event during apoptosis, a type of cell death commonly exhibited by tumor cells responding to treatment. Dissipation of mitochondrial membrane potential can be specifically induced using the K 1 ion channel-opening agent valinomycin and has been used in this study to determine how the loss of mitochondrial membrane potential could influence 18 F-FDG incorporation. Methods: MCF-7 cells were treated with valinomycin for 30 min, inducing loss of mitochondrial membrane potential as determined using flow cytometry with the JC-1 probe. 18 F-FDG incorporation, the initial rate of O-methyl-D-glucose incorporation (a measure of glucose transport), hexokinase activity and subcellular distribution, ATP content using bioluminescence, and lactate production were determined on control and valinomycin-treated cells. Results: A 30-min treatment of MCF-7 cells with 1 mmol of valinomycin per liter resulted in absence of red fluorescence from JC-1, indicative of dissipation of mitochondrial membrane potential. 18 F-FDG incorporation was significantly increased by 30 min of treatment with valinomycin and was still apparent after 3.5 h of incubation. Hexokinase activity and subcellular distribution were not significantly different between control cells and cells treated for 30 min with valinomycin. Glucose transport was moderately though significantly increased, and lactate production was also increased. Conclusion: Loss of mitochondrial membrane potential is associated with increased 18 F-FDG incorporation, glucose transport, and lactate production.

show abstract

Early changes in glucose and phospholipid metabolism following apoptosis induction by IFN‐γ/TNF‐α in HT‐29 cells

Cited by 29 publications

References 41 publications

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

Malignant pleural effusion cells show aberrant glucose metabolism gene expression

Molecular Causes of the Aberrant Choline Phospholipid Metabolism in Breast Cancer

Treatment of Breast Tumor Cells In Vitro with the Mitochondrial Membrane Potential Dissipater Valinomycin Increases 18F-FDG Incorporation

Contact Info

Product

Resources

About