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)

1. The Ca(2+)-antagonism of tetrandrine (TET) on the Ca2+ mobilization in various types of cells were reviewed. Inositol trisphosphate (IP3)-generating drugs were used as Ca(2+)-mobilizing agonists and the effects were compared with those produced by using the microsomal Ca(2+)-ATPase inhibitor thapsigargin (TG), which is a tool for analysing Ca2+ store-regulated Ca2+ entry (capacitative Ca2+ entry). 2. In rat phaeochromocytoma PC12 cells, 100 mumol/L TET abolished high K+ (30 mmol/L)-induced sustained increases in cytoplasmic Ca2+ concentrations ([Ca2+]i) and partially inhibited bradykinin (1 mumol/L)- or TG (100 nmol/L)-induced Ca2+ entry. 3. In NIH/3T3 fibroblasts and rat parotid acinar cells, 100 mumol/L TET abolished Ca2+ entry induced by bombesin (1 mumol/L) and carbachol (100 mumol/L), respectively, or TG (100 nmol/L). However, in the human leukaemia T cell line Jurkat, 100 mumol/L TET did not inhibit Ca2+ entry evoked by either the anti-CD3 antibody OKT3 (10 mg/L) or TG (100 nmol/L). 4. In rat glioma C6 cells, the effects of TET on Ca2+ mobilization were further examined. At a high concentration, TET (300 mumol/L) alone did not affect [Ca2+]i in C6 cells. Tetrandrine inhibited the peak and sustained increases in [Ca2+]i induced by bombesin and TG in a dose-dependent manner. Although TET or TG did not produce increases in IP3, TET did inhibit increases in IP3 produced by bombesin. 5. Our results suggest that the action of TET on Ca2+ entry is dependent on cell types and that TET inhibits both Ca2+ entry from the extracellular medium and Ca2+ release from intracellular stores in rat glioma C6 cells.
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PMID:Tetrandrine as a calcium antagonist. 888 3

Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers, but its effects on gliomas are unknown. In this study, we investigated the effects of tetrandrine on the growth and angiogenesis of rat RT-2 gliomas. We treated RT-2 glioma cells with tetrandrine and then measured cytotoxicity, apoptosis and expression of vascular endothelial growth factor (VEGF). We also examined the cytotoxic effect of tetrandrine on the ECV304 human umbilical vein endothelial cells and the effects of tetrandrine on the in vivo angiogenesis. Tumor size and animal survival were followed in tetrandrine-treated rats with subcutaneous or intracerebral gliomas. Expression of CD31 in tetrandrine-treated gliomas was followed to study its effect on glioma-induced angiogenesis. Tetrandrine had cytotoxic effects and induced apoptosis of glioma cells in a concentration- and time-dependent manner. Tetrandrine also inhibited the expression of VEGF in glioma cells, induced cytotoxicity effect on the ECV304 cells and suppressed the in vivo angiogenesis. Tetrandrine (150 mg/kg/day) had significant antitumor effects on subcutaneous tumors and led to slower tumor growth rate, longer animal survival time and higher animal survival (p < 0.05). Tetrandrine also affected intracerebral tumors and prolonged animal survival (p < 0.05) without affecting survival rate. Immunohistochemical analyses showed that the subcutaneous gliomas from tetrandrine-treated rats had fewer microvessel densities than control rats (p = 0.01). The results demonstrate that tetrandrine is cytotoxic to RT-2 glioma cells, has antitumor effects on subcutaneous and intracerebral gliomas, and inhibits angiogenesis in subcutaneous gliomas. Tetrandrine has potential as a treatment for gliomas.
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PMID:Tetrandrine suppresses tumor growth and angiogenesis of gliomas in rats. 1916 64

Patients with malignant gliomas have poor prognoses, and the majority of the patients have local tumor recurrence after various treatments including surgery, radiotherapy, and chemotherapy. Thus it is mandatory to develop better therapies for treatment of these malignant brain tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers. Tetrandrine affects the cell cycle, production of reactive oxygen species, mitogen-activated protein kinase activity, and reverses multidrug resistance in various cancer cells. Since tetrandrine is a highly lipid-soluble and hydrophobic molecule with a low molecular weight, it may cross the blood brain barrier; thus, it could be used for the treatment of gliomas. Tetrandrine inhibits the large-conductance, calcium-activated potassium (BK) channels and the expression of BK channel has a positive correlation with tumor malignancy grade in human gliomas. Furthermore, tetrandrine also exerts cytotoxic effects, and induces apoptosis and radiosensitization in glioma cells by elimination of radiation-induced cell cycle perturbation. It also has anti-angiogenesis effects in gliomas, and exerts an antitumor effect on subcutaneous and intracerebral gliomas. Tetrandrine is a radiosensitizer and also a multidrug resistance reversing agent. Tetrandrine can probably be combined with radiotherapy or other chemotherapeutic agents to treat gliomas. Nonetheless, it is important to determine the balance between the safety and efficacy of tetrandrine in patients with malignant gliomas before any clinical application.
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PMID:The Potential of Tetrandrine against Gliomas. 2087 81

Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from the root of Hang-Fang-Chi (Stephania tetrandra S. Moore), exhibits broad pharmacological effects, including antitumor activity in various malignant neoplasms. Recently, the beneficial effects of TET on cytotoxicity towards tumor cells, radiosensitization, circumventing multidrug resistance, normal tissue radioprotection, and antiangiogenesis have been examined extensively. However, the potential molecular mechanisms of the effect on glioma of TET are yet unknown. This study is explored to evaluate whether TET can inhibit cell proliferation, invasion, and the possible underlying mechanisms in glioma U87 cell. In the present study, cell proliferation was determined by using the Cell Counting Kit-8 (CCK-8) viability assay. The invasion and migration were evaluated by means of wound-scratch assay and Matrigel-Transwell methods. The mRNA expression and protein expression of ADAM metallopeptidase domain 17 (ADAM17) in glioma cell lines and glioma samples were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, the expression of epidermal growth factor receptor (EGFR)/p-EGFR and AKT/p-AKT was studied to clarify the molecular mechanism. Our results suggested that TET inhibited cell proliferation in a dose- and time-dependent manner, and cell migration and invasion in vitro. In addition, our results indicated that ADAM17 expression significantly increased in glioma compared to nontumored human brain tissue and according to the histopathological grade of glioma. Western blot analysis showed that protein expressions of ADAM17, p-EGFR, and p-AKT were inhibited by TET in U87 cells. These data also suggest that suppression of ADAM17 and downregulation of EGFR-phosphoinositide-3-kinase (PI3K)-AKT signaling pathways may contribute to TET-induced decrease of proliferation, migration, and invasiveness.
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PMID:Effects of tetrandrine on glioma cell malignant phenotype via inhibition of ADAM17. 2418 66

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to possess anti-tumour activity. However, its effects on human glioma remain unknown. In this study, we demonstrated that Tet inhibited human glioma cell growth in vitro and in vivo. It has been hypothesised that Tet inhibits glioma growth by affecting glioma cell survival, proliferation and vasculature in and around the xenograft tumour in the chick CAM model and signal transducer and activator of transcription 3 (STAT3) mediated these activities. Therefore, we conducted a detailed analysis of the inhibitory effects of Tet on cell survival using a TUNEL assay and flow cytometric analysis; on cell proliferation based on the expression of proliferating cell nuclear antigen; and on angiogenesis using a CAM anti-angiogenesis assay. We used western blotting to investigate the role of STAT3 on the anti-glioma activities of Tet. The results revealed that Tet inhibited survival and proliferation in human glioma cells, impaired tumour angiogenesis and decreased the expression of phosphorylated STAT3 and its downstream proteins. In sum, our data indicate that STAT3 is involved in Tet-induced the regression of glioma growth by activating tumour cell apoptosis, inhibiting glioma cell proliferation and inhibiting angiogenesis.
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PMID:Tetrandrine suppresses human glioma growth by inhibiting cell survival, proliferation and tumour angiogenesis through attenuating STAT3 phosphorylation. 2608 59

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.
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PMID:Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation. 2782 69