UMLS:C0017638 - FACTA Search

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Query: UMLS:C0017638 (glioma)
30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim was to exploit simultaneous inhibition of glycolytic and pentose phosphate pathways of energy production for radiosensitization using 2-deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) in transformed mammalian cells. Two human tumour cell lines (cerebral glioma, BMG-1 and squamous carcinoma cells 4197) were investigated. 2-DG and/or 6-AN added at the time of irradiation were present for 4 h after radiation. Radiation-induced cell death (macrocolony assay), cytogenetic damage (micronuclei formation), cell cycle delay (bromodeoxyuridne (BrdU) pulse chase), apoptosis (externalization of phosphotidylserine (PS) by annexin V), chromatin-bound proliferation cell nuclear antigen (PCNA) and cellular glutathione (GSH) levels were investigated as parameters of radiation response. The presence of 2-DG (5 mM) during and for 4 h after irradiation increased the radiation-induced micronuclei formation and cell death, and caused a time-dependent decrease in GSH levels in BMG-1 cells while no significant effects could be observed in 4197 cells. 6-AN (5 microM) enhanced the radiosensitivity of both cell lines and reduced the GSH content by nearly 50% in gamma-irradiated 4197 cells. Combining 2-DG and 6-AN caused a profound decrease in the GSH content and enhanced the radiation damage in both the cell lines by increasing mitotic and apoptotic cell death. Further, the combination (2-DG + 6-AN) enhanced the radiation-induced G2 block, besides arresting cells in S phase and inhibited the recruitment of PCNA. The combination of 2-DG and 6-AN enhances radiation damage by modifying damage response pathways and has the potential for improving radiotherapy of cancer.
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PMID:Radiosensitization by 6-aminonicotinamide and 2-deoxy-D-glucose in human cancer cells. 1607 55

The main cause of the multidrug resistance (MDR) of glioma cells is the overexpression of MRP-1, often associated with high levels of glutathione (GSH). We investigated whether MRP-1-related GSH content can influence (99m)Tc-glucarate entry by comparing its uptake with that of (99m)Tc-sestamibi (MIBI), an MRP- 1 probe, in an in vitro model of a sensitive cell line (U-87-MG) and a resistant derived cell line expressing MRP-1 (U-87-MG-R). Drug resistance was assessed by immunoblotting, GSH measurement, and Alamar Blue assay. To correlate MDR phenotype with tracer accumulation, uptakes were performed with and without modulators and after GSH depletion. Similar accumulation of (99m)Tc-glucarate was observed in the two cell lines, and the use of MDR reversals did not enhance its uptake. Our results clearly demonstrate that (99m)Tc-glucarate uptake is not related to MRP-1 expression or GSH levels. In contrast, (99m)Tc- MIBI accumulation is inversely proportional to the cell MDR phenotype. The combination of (99m)Tc-glucarate and (99m)Tc-MIBI may be a useful tool for the noninvasive detection of malignant sites and their chemoresistance status.
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PMID:MRP-1 protein expression and glutathione content of in vitro tumor cell lines derived from human glioma carcinoma U-87-MG do not interact with 99mTc-glucarate uptake. 1611 87

The present study reports the cytoprotective and antioxidant properties of alcoholic leaf extract of seabuckthorn (SBT) against hypoxia induced oxidative stress in C-6 glioma cells. Exposure of cells to hypoxia for 12 h resulted in a significant increase in cytotoxicity and decrease in mitochondrial transmembrane potential compared to the controls. Further an appreciable increase in nitric oxide and reactive oxygen species (ROS) production was noted which in turn was responsible for fall in intracellular antioxidant levels and GSH/GSSG ratio. There was a significant increase in DNA damage during hypoxia as revealed by comet assay. Pretreatment of cells with alcoholic leaf extract of SBT at 200 mug/ml significantly inhibited cytotoxicity, ROS production and maintained antioxidant levels similar to that of control cells. Further, the leaf extract restored the mitochondrial integrity and prevented the DNA damage induced by hypoxia. These results indicate that the leaf extract of SBT has strong antioxidant and cytoprotective activity against hypoxia induced oxidative injury.
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PMID:Antioxidant activities of seabuckthorn (Hippophae rhamnoides) during hypoxia induced oxidative stress in glial cells. 1618 83

NMDA class of glutamate receptors plays an important role in regulating toxic and plastic responses in CNS. Astrocytes are the predominant cell type in the adult CNS and recent studies have suggested their role in many aspects of CNS function and dysfunction. We report here the protective effect of a subtoxic dose of NMDA in retinoic acid differentiated C6 glioma cell cultures. C6 glioma cell cultures differentiated with retinoic acid (10 microM) were exposed to NMDA (100 microM) or to antagonist MK-801 (200 nM) alone as well as with NMDA and cells were harvested after 24h of treatment to study the expression of HSP70 and for biochemical assay of free radical scavenger system. The protection imparted by a subtoxic dose of NMDA was checked by challenging the differentiated controls as well as NMDA treated and MK-801 treated cultures with a toxic dose of glutamate and subsequently estimating the free radical scavenger system profile. Biochemical analysis revealed a significant increase in the activities of glutathione peroxidase (GPx), copper zinc-superoxide dismutase (CuZnSOD) and reduced glutathione (GSH) content upon exposure to NMDA. No significant change was observed in the level of lipid peroxidation (LPx). A significant increase was observed in HSP70 expression as seen by Western blotting and immunocytofluorescent studies in NMDA treated cultures. Treatment of cultures with MK-801 alone, a non-competitive NMDA receptor antagonist, or pretreatment with MK-801 prior to NMDA exposure prevented the NMDA mediated changes indicating the involvement of NMDA receptors mediated mechanism. The results illustrate the protective effect of a subtoxic dose of NMDA in RA differentiated C6 glioma cell line.
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PMID:HSP70 induction and oxidative stress protection mediated by a subtoxic dose of NMDA in the retinoic acid-differentiated C6 glioma cell line. 1646 83

Accumulation of the branched-chain alpha-keto acids (BCKA), alpha-ketoisocaproic acid (KIC), alpha-keto-beta-methylvaleric acid (KMV), and alpha-ketoisovaleric acid (KIV) and their respective branched-chain alpha-amino acids (BCAA) in tissues and biological fluids is the biochemical hallmark of patients affected by the neurometabolic disorder known as maple syrup urine disease (MSUD). Considering that brain energy metabolism is possibly altered in MSUD, the objective of this study was to determine creatine kinase (CK) activity, a key enzyme of energy homeostasis, in C6 glioma cells exposed to BCKA. The cells were incubated with 1, 5, or 10 mM BCKA for 3 h and the CK activity measured afterwards. The results indicated that the BCKA significantly inhibited CK activity at all tested concentrations. Furthermore, the inhibition caused by the BCKA on CK activity was totally prevented by preincubation with the energetic substrate creatine and by coincubation with the N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, indicating that deficit of energy and nitric oxide (NO) are involved in these effects. In contrast, other antioxidants such as glutathione (GSH) and trolox (soluble Vitamin E) were not able to prevent CK inhibition. In addition, we observed that the C6 cells changed their usual rounded morphology when exposed for 3 h to 10 mM BCKA and that creatine and L-NAME prevented these morphological alterations. Considering the importance of CK for brain metabolism homeostasis, it is conceivable that inhibition of this enzyme by increased levels of BCKA may contribute to the neurodegeneration of MSUD patients.
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PMID:Creatine and antioxidant treatment prevent the inhibition of creatine kinase activity and the morphological alterations of C6 glioma cells induced by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. 1663 2

Studies have shown that ebselen is an antiinflammatory and antioxidative agent. Its protective effect has been investigated in oxidative stress related diseases such as cerebral ischemia in recent years. However, experimental evidence also shows that ebselen causes cell death in several different cell types. Whether ebselen will have a beneficial or detrimental effect on cells under ischemic condition is not known. Herein, we studied the effect of ebselen on C6 glioma cells under oxygen and glucose deprivation (OGD), an in vitro ischemic model. We found that ebselen significantly enhanced cell death after 3 h of OGD as observed by lactase dehydrogenase (LDH) release and cellular morphological changes. Further studies revealed that depletion of cellular glutathione level by the combined action of ebselen and OGD played a role in enhanced cell death as demonstrated by the following evidence: (1) cellular GSH was significantly depleted by the combined effort of ebselen and OGD, compared to that of ebselen or OGD insult alone; (2) exogenous addition of N-acetyl cysteine completely diminished the cell damage induced by ebselen and OGD; (3) supplement of glucose, which provides cellular reducing agents and thus maintains cellular GSH level, to the OGD medium diminished C6 cell damage induced by ebselen. We conclude that depleting cellular glutathione plays an important role in ebselen-induced cell death with OGD. Our results suggest that ebselen can have a beneficial or toxic effect, depending on the availability of GSH.
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PMID:Ebselen induced C6 glioma cell death in oxygen and glucose deprivation. 1669 67

Maple syrup urine disease (MSUD) is an inherited neurometabolic disorder biochemically characterized by the accumulation of the branched-chain alpha-keto acids (BCKA) alpha-ketoisocaproic (KIC), alpha-keto-beta-methylvaleric (KMV) and alpha-ketoisovaleric (KIV) and their respective branched-chain alpha-amino acids in body fluids and tissues. Affected MSUD patients have predominantly neurological features, including cerebral edema and atrophy whose pathophysiology is not well established. In the present study we investigated the effects of KIC, KMV and KIV on cell morphology, cytoskeleton reorganization, actin immunocontent and on various parameters of oxidative stress, namely total antioxidant reactivity (TAR), glutathione (GSH) and nitric oxide concentrations, and on the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in C6 glioma cells. We initially observed that C6 cultivated cells exposed for 3 h to the BCKA (1 and 10 mM) changed their usual rounded morphology to a fusiform or process-bearing cell appearance, while 24 h exposure to these organic acids elicited massive cell death. Rhodamine-labelled phalloidin analysis revealed that these organic acids induced reorganization of the actin cytoskeleton with no modifications on total actin content. It was also observed that 3h cell exposure to low doses of all BCKA (1 mM) resulted in a marked reduction of the non-enzymatic antioxidant defenses, as determined by TAR and GSH measurements. In addition, KIC provoked a reduced activity of SOD and GPx, whereas KMV caused a diminution of SOD activity. In contrast, CAT activity was not modified by the metabolites. Furthermore, nitric oxide production was significantly increased by all BCKA. Finally, we observed that the morphological features caused by BCKA on C6 cells were prevented by the use of the antioxidants GSH (1.0 mM), alpha-tocopherol (trolox; 10 microM) and Nomega-nitro-L-arginine methyl ester (L-NAME; 500 microM). These results strongly indicate that oxidative stress might be involved in the cell morphological alterations and death, as well as in the cytoskeletal reorganization elicited by the BCKA. It is presumed that these findings are possibly implicated in the neuropathological features observed in patients affected by MSUD.
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PMID:Morphological alterations and induction of oxidative stress in glial cells caused by the branched-chain alpha-keto acids accumulating in maple syrup urine disease. 1682 90

Molecular and genetic signatures may predict brain tumor behavior and may soon guide tumor classification, diagnosis, and tumor-specific treatment strategies. Free oxygen radicals (FOR) are thought to take part in oncogenesis and cellular differentiation. This article explored the state of FORs and antioxidant system in patients with cerebral tumor. The serum concentrations of malondialdehyde (MDA), catalase, and glutathione peroxidase (GSH-Px) enzyme activities were measured in the serum of 35 patients with cerebral tumors (21 glioma, 14 meningioma) and 11 controls. MDA measurement was done with fluorometric method and catalase and GSH-Px enzyme activities were done with photometric method. Mean serum MDA levels, catalase, and GSH-Px enzyme activities were significantly higher for both glial and meningiomal tumor cases when compared to controls (p < .05). There is no significant difference between glioma and meningioma groups in terms of the aforementioned parameters (p > .05). In conclusion, lipid peroxidation and antioxidant enzymes as assessed by MDA, catalase, and GSH-Px were increased in patients with brain tumors, for this respect there is no difference between gliomas and meningiomas.
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PMID:Lipid peroxidation in patients with brain tumor. 1686 Nov 59

Different cell types response differently to toxic insult. In a previous study, it was demonstrated that the C6 glioma cell is more sensitive to Cd induced oxidative stress than the HepG2 cells. To explain the difference between the two cell lines in their response to oxidative stress, it was hypothesized that the activity of glutathione metabolizing enzymes may be different. The objective of this study is to determine the activities of glutathione peroxidase (GPx) and glutathione reductase (GR) in the two cell lines and to explain how these differences may affect the susceptibility of the two cells to oxidative stress. In the HepG2 cells, the activity of GPx was 2.24+/-0.18 micromol/mg protein/min and that for GR was 5.63+/-0.58 micromol/mg protein/min. For the C6 glioma cells, GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11 micromol/mg protein/min, respectively. Using the kinetic equilibrium: K(eq)=([GSSG]x[NADPH]x[H(+)])/([GSH](2)x[NADP(+)]), and the GSH/GSSG previously published (HepG2: 2.6 and C6 glioma: 3.6), resting NADPH/NADP(+) for the cell lines were calculated. The results showed that NADPH/NADP(+) for HepG2 cells (17.8) is higher than that in the C6 glioma cells (10.8). These data supported the notion that the reducing power (NADPH/NADP(+)) in the HepG2 cells is higher than that in the C6 glioma cell and thus, the later would be more susceptible to oxidative stress. The results also suggested that besides GSH/GSSG, the activities of GPx and GR are important in predicting tissue redox state. Applying this hypothesis to animal tissues, the ratio of the activities of the two enzymes in mouse liver, cerebral cortex, hippocampus and cerebellum were measured. It was demonstrated that the activities of GPx and GR were different in the different tissues studied. The possible correlation between enzymatic activities and the redox state in the different tissues were discussed.
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PMID:Glutathione peroxidase and glutathione reductase activities are partially responsible for determining the susceptibility of cells to oxidative stress. 1688 53

We investigated the in vitro effect of 3-hydroxykynurenine (3HKyn), 3-hydroxyanthranilic acid (3HAA), kynurenine (Kyn) and anthranilic acid (AA) on various parameters of oxidative stress in rat cerebral cortex and in cultured C6 glioma cells. It was demonstrated that 3HKyn and 3HAA significantly reduced the thiobarbituric acid-reactive substances (TBA-RS) and chemiluminescence measurements in rat cerebral cortex, indicating that these metabolites prevent lipid peroxidation in the brain. In addition, GSH spontaneous oxidation was significantly prevented by 3HAA, but not by the other kynurenines in cerebral cortex. We also verified that 3HKyn and 3HAA significantly decreased the peroxyl radicals induced by the thermolysis of 2,2'-azo-bis-(2-amidinopropane)-derived peroxyl radicals, and to a higher degree than the classical peroxyl scavenger trolox. 2-Deoxy-d-ribose degradation was also significantly prevented by 3HKyn, implying that this metabolite was able to scavenge hydroxyl radicals. Furthermore, the total antioxidant reactivity of C6 glioma cells was significantly increased when these cells were exposed from 1 to 48h to 3HKyn, being the effect more prominent at shorter incubation times. TBA-RS values in C6 cells were significantly reduced by 3HKyn when exposed from 1 to 6h with this kynurenine. However, C6 cell morphology was not altered by 3HKyn. Finally, we tested whether 3HKyn could prevent the increased free radical production induced by glutaric acid (GA), the major metabolite accumulating in glutaric acidemia type I, by evaluating the isolated and combined effects of these compounds on TBA-RS levels and 2',7'-dihydrodichlorofluorescein (DCFH) oxidation in rat brain. GA provoked a significant increase of TBA-RS values and of DCFH oxidation, effects that were attenuated and fully prevented, respectively, by 3HKyn. The results strongly indicate that 3HKyn and 3HAA behave as antioxidants in cerebral cortex and C6 glioma cells from rats.
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PMID:In vitro evidence for an antioxidant role of 3-hydroxykynurenine and 3-hydroxyanthranilic acid in the brain. 1695 77

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