Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the impact of purified bacterially synthesized GST-MDA-7 (IL-24) and ionizing radiation on the proliferation and survival of nonestablished human glioblastoma multiforme (GBM) cells. Glioma cell types expressing mutated PTEN and p53 molecules, activated ERBB1VIII, overexpressing wild type ERBB1 or without receptor overexpression were selected. In MTT assays, GST-MDA-7 caused a dose-dependent reduction in the proliferation of nonestablished glioma cells; however only at higher concentrations did GST-MDA-7 reduce cell viability. The anti-proliferative and cytotoxic effects of GST-MDA-7 were enhanced by radiation in a greater than additive fashion that correlated with JNK1/2/3 activation. The reduction in cell growth and enhancement in cell killing by the combination of GST-MDA-7 and radiation were blocked by an ROS scavenger, N-acetyl cysteine (NAC), a JNK1/2/3 inhibitor SP600125, a pan-caspase inhibitor (zVAD) and by an inhibitor of caspase 9 (LEHD), but not by an inhibitor of caspase 8 (IETD). Low concentrations of either GST-MDA-7 or radiation reduced clonogenic survival, however colony formation ability was significantly further decreased when the two treatments were combined, which was also blocked by inhibition of caspase 9 function. In general agreement with activation of the intrinsic caspase pathway, cell death correlated with reduced BCL-XL expression and with increased levels of the pro-apoptotic proteins BAD and BAX. Inhibition of caspase 9 after combination treatment blunted neither JNK1/2/3 activation nor the enhanced expression of BAD and BAX, but did block caspase 3 cleavage, reduced expression of BCL-XL and inhibition of ERK1/2 activity. In contrast, incubation with NAC blocked JNK1/2/3 activation and cell killing, but not the increases in BAD and BAX expression. These findings argue that after combination treatment JNK1/2/3 activation is a primary pro-apoptotic event and loss of BCL-XL expression and ERK1/2 activity are secondary caspase-dependent processes. This data also argues that GST- MDA-7 induces two parallel pro-apoptotic pathways via ROS-dependent and -independent mechanisms. Infection of primary human astrocytes with a recombinant adenovirus to express MDA-7, Ad.mda-7, but not infection with either Ad.cmv or Ad.mda-7SP- lacking MDA-7 secretion, resulted in the suppression of GBM cell colony formation in soft agar overlay assays, an effect that was enhanced in a greater than additive fashion by radiation. Collectively, our findings demonstrate that MDA-7 reduces proliferation and enhances the radiosensitivity of nonestablished human GBM cells in vitro, and when grown in 3 dimensions, and that sensitization occurs independently of basal EGFR/ERK1/2/AKT activity or the functions of PTEN and p53.
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PMID:MDA-7 regulates cell growth and radiosensitivity in vitro of primary (non-established) human glioma cells. 1532 89

The potential cytoprotective effects of estrogen in the brain are of special interest in aging, neurodegenerative diseases, exposure to toxins, and trauma. Estrogen effects on neurons have been widely explored, but less is known about estrogen effects on glia. Glial cells are primary targets of ammonia toxicity, which arises from liver disease or failure (such as from cirrhosis in alcoholics), urea cycle disorders, or inborn errors of metabolism. We examined the ability of estrogen to protect glial cells from ammonium chloride toxicity using an in vitro model system. C6-glioma cells in later passage have many astrocytic characteristics and provided a convenient and well established model system for this work. When C6-glioma cells were exposed to 15 mM ammonium chloride, we observed major cell death (only 32% cell survival relative to control) within 72 h. Pretreatment with 17beta-estradiol (10 microM) significantly protected C6-glioma cells from ammonia toxicity (99% cell survival relative to control). In addition to enhancing the viability of C6-glioma cells against ammonia challenge, estrogen pretreatment was also found to protect mitochondrial function as assayed using the MTT reduction assay. Mitochondrial function was reduced to 39% of control levels in ammonia-challenged cultures and was mostly protected by estrogen (72% of control levels). The findings are potentially relevant for the development of therapeutic strategies to protect glial cells against ammonia toxicity resulting from hepatic failure or other causes.
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PMID:Cytoprotective effect of estrogen on ammonium chloride-treated C6-glioma cells. 1520 65

Well known antioxidants-coumarins (7,8-dihydroxy-4-methyl coumarin-DHMC and 7,8-diacetoxy-4-methyl coumarin-DAMC) and flavonoids (quercetin-Q and quercetin penta-acetate-QPA) were investigated for their pro-oxidant effects in two human tumor cell lines. The breast carcinoma cell line (MDA-MB-468) was found to be more sensitive to treatment by the drugs-DAMC, Q and QPA at 10 microM than the glioma cell line (U-87MG), while DHMC was non toxic in both cell lines at this concentration. In MDA-MB-468 distinct growth inhibition was observed by 48 hr post treatment. Paradoxically, an increase in the formazan production was revealed by MTT assay at this time indicating an increase in the production of free radicals. An increase in the levels of reactive oxygen species (ROS) was also confirmed by DCFH-DA assay. In cells treated with DAMC, Q and QPA an increase in the percentage of cells with the hypodiploid DNA content was suggestive of apoptotic cell death. Taken together, these results suggest that an increase in oxidative stress caused by the pro-oxidant action of these drugs is responsible for cell death.
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PMID:Suicidal oxidative stress induced by certain antioxidants. 1533 96

Brain ischemia brings about hypoxic insults. Hypoxia is one of the major pathological factors inducing neuronal injury and central nervous system infection. We studied the involvement of mitogen-activated protein (MAP) kinase in hypoxia-induced apoptosis using cobalt chloride in C6 glioma cells. In vitro cytotoxicity of cobalt chloride was tested by MTT assay. Its IC(50) value was 400 microM. The DNA fragment became evident after incubation of the cells with 300 microM cobalt chloride for 24 h. We also evidenced nuclear cleavage with morphological changes of the cells undergoing apoptosis with electron microscopy. Next, we examined the signal pathway of cobalt chloride-induced apoptosis in C6 cells. The activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) started to increase at 1 h and was activated further at 6 h after treatment of 400 M cobalt chloride. In addition, pretreatment of PD98059 inhibited cobalt chloride-induced apoptotic cell morphology in Electron Microscopy. These results suggest that cobalt chloride is able to induce the apoptotic activity in C6 glioma cells, and its apoptotic mechanism may be associated with signal transduction via MAP kinase (ERK 1/2).
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PMID:Cobalt chloride-induced apoptosis and extracellular signal-regulated protein kinase 1/2 activation in rat C6 glioma cells. 1546 37

Glioblastoma multiforme is characterized as highly invasive and rapidly growing astrocytomas, and scientists have sought for efficient treatment against malignant gliomas for a long time. Therefore, we compared the respond of rat glioma (C6) and glioblastoma multiforme cells derived from two patients to vitamins K1, K2 and K3. The cells were exposed to 100, 250, 500, 750 and 1000 microM of vitamins K1 and K2, and 1, 10, 25, 50, 75 and 100 microM of vitamin K3 for 24 hours in an incubator atmosphere of 5% CO2, 37 degrees C and 100% humidity. Cell viability was estimated by MTT assay. Vitamin K1 showed no growth effect on all the glioma cells examined. Vitamin K2 did not cause any change in number of C6, however induced growth inhibition in a dose-dependent manner on glioblastoma multiforme. The IC50 values of vitamin K2 were 960 microM and 970 microM for glioblastoma multiforme, respectively. Vitamin K3 had also growth inhibitory effect in a dose-dependent manner on both C6 and glioblastoma multiforme. The IC50 values were 41 microM, 24 microM and 23 microM for vitamin K3, respectively. We concluded that vitamin K3 is more effective than vitamin K2 for inhibition of cancer cell growth, and might have an alternative value as an anticancer drug against glioblastoma multiforme.
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PMID:Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro. 1550 63

In this study, the possible effects of MgSO4 and lazaroid (U-83836E) on glutamate toxicity on glial cells were investigated. C6 and human glioblastoma multiforme cells derived from two patients were grown in an incubator. First, determined IC50 dose of L-glutamate (L-glu) was given for 24 hours and removed, and then respective MgSO4 or U-83836E doses were added to the culture medium. After 24 hours 3-(4,5-Dimethylthyazol-2-yl)-2,5-diphenyltetrazolium bromide, thiazolyl blue (MTT) test was applied. When compared to the L-glu-treated group, MgSO4 at the dose of 0.01 mM induced C6 and human glioma cell growth by 17%, 15% and 5%, respectively. At the dose of 1 microM U-83836E also increased C6 and human glioma cell growth by 12%, 13% and 5%, respectively. In conclusion, although MgSO4 and U-83836E do not strongly block glutamate-induced cell death, it is suggested that reduction of Mg2+ ions and free radical production may have a role in glutamate toxicity on glial cells.
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PMID:MgSO4 and lazaroid (U-83836E) partially protects glioma cells against glutamate toxicity in vitro. 1558 62

To investigate the anti-vasculature effects and the anti-glioma effects of attenuated Salmonella typhimurium vaccine strain expressing VEGFR2 (flk-1) gene, plasmid pcDNA3.1-flk1 was constructed and electro-transfected into live attenuated Salmonella typhimurium strain SL7207. Mouse models of intracranial G1261 glioblastoma were treated with an orally administered attenuated Salmonella typhimurium expressing flk-1 gene. The survival period was recorded and vessel density was observed by immunofluorescence. CTLs activity was measured by MTT assay. Our results showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could significantly inhibit glioblastoma growth, reduce vessel density, prolong the survival period and improve the survival rate in these mice. The flk-1 specific CTLs activity was increased obviously after the vaccination. Our study showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could break peripheral immune tolerance a in glioma gainst this self-antigen and kill endothelial cells by the orally administered vaccine and can be used for both prophylactic and therapeutic purposes.
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PMID:Anti-angiogenesis effect on glioma of attenuated Salmonella typhimurium vaccine strain with flk-1 gene. 1558 6

GM3, the simplest ganglioside, modulates cell adhesion, proliferation and differentiation in the central nervous system and exogenously added GM3 regulates cell-cell and cell-extracellular matrix adhesion and induces apoptosis. To assess the anti-tumor action of exogenous GM3, we examined its effect on the proliferation and invasion of glioma cells. Its inhibitory effect on cell proliferation was demonstrated in vitro by 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and in vitro in rats with meningeal gliomatosis whose survival was significantly prolonged by the intrathecal injection of GM3. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay revealed that GM3 induced glioma cell apoptosis in vitro and in vitro. In rat brain slice cultures, GM3 suppressed the invasion of glioma cells; this effect manifested earlier than the inhibition of cell proliferation and before apoptosis induction. Our results suggest exogenous GM3 as a potential therapeutic agent in patients with glioma requiring adjuvant therapy.
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PMID:Ganglioside GM3 inhibits proliferation and invasion of glioma. 1569 Jan 23

Malignant glioma invasion into the surrounding brain tissue is still a major problem for any therapeutical methods. Matrix metalloproteinases (MMPs) have been implicated as important factors in this pathological process. In this study, one of the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin was employed to investigate the effect of inhibition of cell invasion mediated by MMP-2 and MMP-9 in human malignant glioma cell lines, A172, U87MG, U251MG, and U373MG in vitro. MTT assay was firstly examined to determine non-cytotoxic dose range, then gelatin zymography, matrigel invasion assay, migration assay and MMP-2 activity assay for 24 h exposure in indomethacin were employed to assess the inhibitory effect of indomethacin. MTT assay revealed that dose with 0, 50, and 500 microM/ml were non-cytotoxic. Zymography demonstrated: (a) expression of MMP-2 and MMP-9 activity was downregulated along with elevated dose of indomethacin. (b) MMP-2 activity that changed from pro-MMP-2 to active form of MMP-2 in supernatants of cell lines could not be inhibited by indomethacin. Invasion assay disclosed that the number of invading cells through the matrigel were significantly decreased in a dose dependent manner. Migration assay indicated indomethacin did not affect cells migration. MMP-2 activity assay showed the total and active MMP-2 secretion was suppressed by 500 microM/ml of indomethacin. Our present study is the first report on inhibitive effect of indomethacin mediated by MMP-2 and MMP-9 in invasion assay of glioma cell lines. The current study suggested that non-cytotoxic level of indomethacin was able to reduce the cell invasion of malignant gliomas mediated by MMP-2 and MMP-9, but it did not affected on cell motility. It also lowered down the activity of MMP-2 and MMP-9, and could reduce of MMP-2 secretion of cell lines. Thus, high concentration of indomethacin within non-cytotoxic dose might offer a new therapeutic strategy to impair cell invasion of gliomas.
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PMID:Inhibition of cell invasion by indomethacin on glioma cell lines: in vitro study. 1580 68

Histone deacetylase (HDAC) inhibitors have both apoptotic and differentiating effects on various tumor cells. However, the mechanisms underlying the effect of HDAC inhibitors remain unclear. In this study, we investigated the function of anti-proliferative effects of HDAC inhibitors, N-butyric acid and trichostatin A, on human malignant glioma cell lines, U251-MG and D54. MTT assay showed a dose-dependent inhibition of cellular proliferation in both cell lines. Cell cycle analysis revealed increased sub-G1 population in both lines, and G1 arrest only in U251-MG cells. Induction of apoptosis was also supported by the occurrence of DNA fragmentation in tumor cells treated with HDAC inhibitors. Furthermore, caspase inhibition assay indicated that HDAC inhibitor-induced apoptosis was caspase-dependent. Neither mitochondrial membrane potential nor the expression of caspase-9 was changed by treatment with HDAC inhibitors, suggesting the possibility that HDAC inhibitor-induced apoptosis was not mediated by the mitochondrial cell death pathway. On the other hand, immunoblot assay confirmed increased expression of caspase-8 in both lines, and elevation of p21 but not p27 protein in U251-MG cells following HDAC inhibitor treatment. Taken together, the HDAC inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis with or without p21-mediated G1 arrest in human malignant glioma cells.
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PMID:Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells. 1580 27


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