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)

Panaxydol is a naturally occurring non-peptidyl small molecule isolated from the lipophilic fractions of Panax notoginseng, a well-known Chinese traditional medicine. Previous studies have shown that panaxydol inhibited the growth of various kinds of malignant cell lines. To date, there has been no report concerning the effect of panaxydol on cell growth inhibition in glioma cells. In this paper, we examined panaxydol's antiproliferation and proapoptotic effects on rat C6 glioma cells and investigated its mechanism. Cell growth inhibition of panaxydol was determined by MTT reduction assay. Apoptosis of cells was measured by both Hoechst 33258 staining and Annexin V analysis. It was found that panaxydol markedly inhibited proliferation of C6 cells in a dose-dependent manner with ID(50) of 40 microM. The cell apoptosis was observed at 48 h in the presence of panaxydol. In concert with these findings, Western blot analysis showed a decreased expression of bcl-2 and increased levels of Bax and caspase-3 in C6 cells treated by panaxydol. In conclusion, panaxydol has profound effects on growth and apoptosis of C6 cells, suggesting that panaxydol may be a potential candidate for the treatment of malignant gliomas.
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PMID:Induction of apoptosis in rat C6 glioma cells by panaxydol. 1732 Apr 24

Multiple genetic aberrations in human gliomas contribute to their highly infiltrative and rapid growth characteristics. Focal adhesion kinase (FAK) regulates tumor migration and invasion. Insulin-like growth factor-I receptor (IGF-IR), whose expression correlates with tumor grade, is involved in proliferation and survival. We hypothesized that inhibiting the phosphorylation of FAK and IGF-IR by NVP-TAE226 (hereafter called TAE226), a novel dual tyrosine kinase inhibitor of FAK and IGF-IR, would suppress the growth and invasion of glioma cells. In culture, TAE226 inhibited extracellular matrix-induced autophosphorylation of FAK (Tyr(397)). TAE226 also inhibited IGF-I-induced phosphorylation of IGF-IR and activity of its downstream target genes such as MAPK and Akt. TAE226 retarded tumor cell growth as assessed by a cell viability assay and attenuated G(2)-M cell cycle progression associated with a decrease in cyclin B1 and phosphorylated cdc2 (Tyr(15)) protein expression. TAE226 treatment inhibited tumor cell invasion by at least 50% compared with the control in an in vitro Matrigel invasion assay. Interestingly, TAE226 treatment of tumor cells containing wild-type p53 mainly exhibited G(2)-M arrest, whereas tumor cells bearing mutant p53 underwent apoptosis. Induction of apoptosis by TAE226 was substantiated by detection of caspase-3/7 activation and poly(ADP-ribose) polymerase cleavage and by an Annexin V apoptosis assay. More importantly, TAE226 treatment significantly increased the survival rate of animals in an intracranial glioma xenograft model. Collectively, these data show that blocking the signaling pathways of FAK and IGF-IR with TAE226 has the potential to be an efficacious treatment for human gliomas.
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PMID:Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. 1743 Nov 14

Thymosin fraction-5 (TF5) is a protein preparation of the bovine thymus. TF5 stimulates many assays of T cell-mediated immunity. We found that TF5 substantially suppressed proliferation of the rat C6 glioma and MMQ pituitary adenoma cell lines. Our current research using the promyelocytic cell line HL-60 suggests that TF5 also prevents proliferation of human myeloid leukemia cells. Our objective is the purification and chemical characterization of TF5 peptide components responsible for inhibition of HL-60 proliferative capacity. Using the inhibition of HL-60 cell proliferation, we have chemically characterized TF5 using fast protein liquid chromatography (FPLC), reversed-phase high-performance liquid chromatography (RP-HPLC), and high-performance capillary electrophoresis (HPCE). Vital dye-exclusion, oxidative metabolism of chromogenic dyes, and clonogenic growth profiles were used to determine rates of HL-60 proliferation. Our results identified an approximately 6000 Da component of TF5 capable of inducing HL-60 growth arrest. Synchronized HL-60 cells exposed to TF5 and its various constituents were subjected to cytometric analysis by flow cytometry. TF5-treated HL-60 cells had an increased subdiploid faction (i.e., sub-G1) compared to control cells. TF5 also increased Annexin V staining in randomly cycling HL-60 cells. Thus, a TF5 subfraction possesses growth-suppressive activity for human myeloid neoplasms. Our results indicate that this effect is characterized by at least one hallmark of apoptosis. Future clinical management strategies for certain leukemias may involve the use of thymic peptides.
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PMID:Thymosin fraction-5 possesses antiproliferative properties in HL-60 human promyelocytic leukemia cells: characterization of an active peptide. 1760 Feb 87

This study investigated the effect of triptolide, derived from the traditional Chinese herb Tripterygium wilfordii, on the growth of glioblastoma multiforme (GBM) cells. Glioma cell lines U251MG and U87MG and normal human fetal astrocytes were exposed to various concentrations of triptolide, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and colony formation assays were used to measure cell growth and survival. Cell apoptosis was determined using annexin V. Levels of the oncogenic transformation-related proteins Ras-guanosine triphosphate (Ras-GTP), extracellular signal-regulated kinase (ERK) and Akt were determined by Western blotting. Triptolide caused a dose-dependent decrease in proliferation and increase in apoptosis in the glioma cell lines. Since U87MG has a wildtype p53 gene while U251MG harbours a mutated p53 gene, these results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. Treatment of GBM cells with triptolide attenuated both the Ras/ERK and the Ras/Akt signalling pathways. This could provide a theoretical basis for triptolide treatment in GBM, but further animal studies and clinical research are necessary.
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PMID:Inhibitory effect of triptolide on glioblastoma multiforme in vitro. 1769 26

Rose Bengal (RB) is a very efficient photosensitizer which undergoes inactivation of its photophysical and photochemical properties upon addition of a quencher group-i.e. acetate-to the xanthene rings. The resulting RB acetate (RB-Ac) derivative behaves as a fluorogenic substrate: it easily enters the cells where the native photoactive molecule is restored by esterase activities. It is known that the viability of RB-Ac-loaded cells is strongly reduced by light irradiation, attesting to the formation of intracellular RB. The aim of this study was to identify the organelles photodamaged by the intracellularly formed RB. RB-Ac preloaded rat C6 glioma cells and human HeLa cells were irradiated at 530 nm. Fluorescence confocal imaging and colocalization with specific dyes showed that the restored RB molecules redistribute dynamically through the cytoplasm, with the achievement of a dynamic equilibrium at 30 min after the administration, in the cell systems used; this accounted for a generalized damage to several organelles and cell structures (i.e. the endoplasmic reticulum, the Golgi apparatus, the mitochondria, and the cytoskeleton). The multiple organelle damage, furthermore, led preferentially to apoptosis as demonstrated by light and electron microscopy and by dual-fluorescence staining with FITC-labelled annexin V and propidium iodide.
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PMID:Apoptosis in tumour cells photosensitized with Rose Bengal acetate is induced by multiple organelle photodamage. 1784 39

The cell survival activity of human glioma cells is largely dependent on autocrine fibroblast growth factor (FGF) signaling. Caspases, a family of cysteine proteases, play an integral part in the execution phase of apoptosis. To better understand the mechanism of resistance to apoptosis in human glioma cells, we investigated the effect of a blockade of endogenous FGF signaling through the expression of the dominant negative type I FGF receptor (DNFGFR) in U251MG cells. The cells were infected with adenovirus vector expressing DNFGFR (AdDNFGFR) and apoptosis was semi-quantified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method and flow cytometric annexin V assay. The activation of caspase-3, -8, and -9, the activation of Akt, a serine/threonine protein kinase, and the cleavage of poly(ADP-ribose) polymerase (PARP) were analyzed by immunoblotting. The infection with AdDNFGFR (multiplicity of infection of 200) induced marked apoptosis, along with a down-regulation of akt phosphorylation, and activation of caspase-9 and -3, but not -8. By contrast, LacZ virus (a control) had minimal effects. The level of the cleaved form of PARP was increased in a time-dependent fashion, and this increase was inhibited by adding Z-DEVD-FMK, a caspase-3 inhibitor, and Z-LEHD-FMK, a caspase-9 inhibitor. Moreover, ultraviolet exposure (100 J/m(2)) induced apoptosis and caspase-8, but not caspase-9, activation. Our data suggested that the induction of apoptosis through the inhibition of endogenous FGF signaling is caspase-9 pathway- dependent. The suppression of this or other specific anti-apoptotic pathways may lead to genetic or pharmacological manipulations that favorably modulate the malignant behavior of human gliomas.
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PMID:Caspase-9 pathway activation by inhibiting endogenous fibroblast growth factor signaling in human glioma cells. 1820 70

Rat C6 glioma is a chemo-resistant experimental brain tumor that is difficult to treat with various drug combinations. Previous studies suggested that imatinib mesylate (Gleevec) is effective in pre-clinical trials for glioblastoma. Also, chlorimipramine (Anafranil) is an anti-depressant drug in use in the clinic and shown to have anti-neoplastic activity. We hypothesized that treatment of resistant C6 glioma with combination of imatinib and chlorimipramine may potentiate cytotoxicity and reverse resistance. C6 glioma was examined both as monolayer and as spheroid cultures. Several experimental designs were examined all of which showed synergistic activity albeit at different time kinetics. Combination treatment resulted in inhibition of cell growth and enhanced cell death as determined by dye exclusion. Further, the combination treatment resulted in significant induction of apoptosis as determined by Annexin V-FITC and PI. Also, there was inhibition of DNA synthesis and cAMP. Altogether, these findings supported the anti-proliferative and cytotoxic effects of the combination treatment. Morphological studies were also performed using transmission and scanning electron microscopy. Significant synergistic apoptosis was detected by the combination treatment in both the monolayers and spheroid cultures. There was also a synergistic effect in autophagy by the combination. Several altered morphological features were noted by both the individual compound and enhanced by the combination treatment. The present findings support our hypothesis and demonstrate the potentiation of cytotoxicity by the combination of imatinib and chlorimipramine in C6 glioma. Further, the findings suggest the potential clinical application of the combination in the treatment of drug-resistant glioma.
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PMID:Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma. 1836 Jul 10

Matrine, one of the main components extracted from Sophora flavescens Ait, has a wide range of pharmacological effects including anti-tumor activities on a number of cancer cell lines. This study has investigated whether matrine could also display anti-tumor action on rat C6 glioma cells. Exposure of C6 cells to matrine resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner, as measured by the MTT assay and Flow cytometry. The Annexin V/PI staining further detected the apoptotic cells at both early and late phases of apoptosis. We used AO/EB staining to examine the programmed cell death of matrine-treated C6 cells, and showed that the death rate detected by AO/EB staining was higher than the apoptosis rate measured by Annexin V/PI staining, suggesting that autophagy, the Type II programmed cell death, may be involved in matrine-induced cell death, which was further confirmed by electronic microscopy. To explore the molecular mechanism, an apoptosis real-time PCR array was performed, which has demonstrated that 57 genes were at least 2-fold upregulated, and 11 genes were at least 2-fold downregulated in matrine-treated C6 cells, compared with untreated cells. However, the gene expression profiles could only partly and roughly explain molecular mechanisms of apoptosis and autophagy in matrine-treated C6 cells, thus further investigations are required to confirm the specific molecular pathways and related molecules responsible for the programmed cell death.
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PMID:Matrine induces programmed cell death and regulates expression of relevant genes based on PCR array analysis in C6 glioma cells. 1839 46

Enzastaurin (LY317615.HCI), a protein kinase C (PKC)-beta inhibitor, has a radiosensitising effect on 4T1 murine breast cancer and human glioma cells; however, the exact mechanism of this action has not been evaluated. The present study investigated the effects of enzastaurin and gamma irradiation on PKC activity in MCF-7 human breast cancer cells in vitro and in vivo. Enzastaurin (5 microM) in combination with irradiation (2-8 Gy) produced a synergistic decline in MCF-7 clonogenic cell survival. Analysis of MCF-7 cells stained with Annexin V and 7-aminoactinomycin D showed a dose-dependent increase in apoptosis in response to enzastaurin (3, 5 and 7 microM) and irradiation (10 Gy) compared to irradiation alone. This pro-apoptotic effect was confirmed by increases in caspase-3 and -9 activity. In a MCF-7 xenograft model, irradiation with 25 Gy increased PKC-alpha activity by 2.5-fold compared to untreated controls, whereas PKC-epsilon and -betaII activity was increased by 1.8-fold. Radiation-induced activation of all three anti-apoptotic isoforms of PKC was reversed by pre-treatment with enzastaurin (75 mg/kg, twice daily for 3 days). We conclude that enzastaurin has a radiosensitising effect on MCF-7 human xenograft tumours through the reversal of anti-apoptotic activation of PKC isoforms.
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PMID:Enzastaurin renders MCF-7 breast cancer cells sensitive to radiation through reversal of radiation-induced activation of protein kinase C. 1844 27

Titanium dioxide (TiO(2)) is thought to be a photocatalytic agent excited by UV light. Our aim was to investigate the photocatalytic antitumor effect of water-dispersed TiO(2) nanoparticles on C6 rat glioma cells and to evaluate the treatment responses by the spheroid models. Water-dispersed TiO(2) nanoparticles were constructed by the adsorption of chemical modified polyethylene glycol (PEG) on the TiO(2) surface (TiO(2)/PEG). Each monolayer and spheroid of C6 cells was coincubated with various concentrations of TiO(2)/PEG and subsequently irradiated with UV light. Damage of the cells and spheroids was evaluated sequentially by staining with the fluorescent dyes. The cytotoxic effect was correlated with the concentration of TiO(2)/PEG and the energy dose of UV irradiation. More than 90% of cells were killed after 13.5 J cm(-2) of UV irradiation in the presence of 500 microg mL(-1) TiO(2)/PEG. The irradiated spheroids in the presence of TiO(2)/PEG showed growth suppression compared with control groups. In TiO(2)/PEG-treated spheroids, the number of Annexin V-FITC-stained cells gradually increased during the first 6 h, and subsequently propidium iodide-stained cells appeared. The results of this study suggest that newly developed photoexcited TiO(2)/PEG have antitumoral activity. Photodynamic therapy utilizing this material can be a clue to a novel therapeutic strategy for glioma.
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PMID:Novel photodynamic therapy using water-dispersed TiO2-polyethylene glycol compound: evaluation of antitumor effect on glioma cells and spheroids in vitro. 2049 66


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