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)

N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) is known to be a potent calmodulin antagonist and inhibitor of calmodulin-dependent protein kinases. W-7 and 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7) are inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. In C6 glioma cells, W-7 and not H-7 inhibited dose-dependently acid sphingomyelinase, a result indicating the modulation of this lysosomal enzyme by a calmodulin-dependent system. Other lysosomal enzymes, such as beta-glucosidase, alpha-galactosidase, and arylsulfatase A, were unaffected by W-7 and H-7, a finding indicating a selective effect of W-7 on sphingomyelinase.
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PMID:Calmodulin antagonist W-7 inhibits lysosomal sphingomyelinase activity in C6 glioma cells. 254 Feb 82

Cationic amphiphilic drugs, which include tricyclic antidepressants, have been shown to give rise to lipidoses under experimental conditions, with a general increase of lipids especially phospholipids. We report here an early and important decrease in sphingomyelinase activity in C6 glioma cells cultured in the presence of imipramine or desipramine at final concentrations of 0.01 and 0.05 mM. The effect was both dose-dependent and time-dependent and was observed before any lipid accumulation. Cerebroside beta-glucosidase and cerebroside beta-galactosidase had normal activities under the same experimental conditions and thus there was no general effect on membrane-bound sphingolipid hydrolases. A decrease of sphingomyelinase activity has been previously reported for two amphiphilic compounds, perhexiline maleate and AY 9944. These results suggest a potential function of sphingomyelinase in the mode of action of these drugs.
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PMID:Effect of tricyclic antidepressants on sphingomyelinase and other sphingolipid hydrolases in C6 cultured glioma cells. 630 26

We present here a suicide therapy against malignant gliomas based on the transfer to tumor cells of a gene encoding a beta-glucosidase, linamarase (lis), which in the presence of the innocuous substrate linamarin (lin) produces cyanide, blocking the mitochondrial respiratory chain. Dog glioma cells carrying the lis gene are thus sensitive to lin (IC(50) of 250 microg/mL at 48 hours) and cell death is accompanied by mitochondrial fission and ATP depletion. The combination of lis/lin with an otherwise nontoxic level of glucose oxidase (GO) enhances the therapeutic potential (IC(50) of 50 microg/mL at 48 hours). GO produces hydrogen peroxide, inducing oxidative damage and increasing cellular stress. We show here the antitumoral effect of the lis/lin/GO therapy in a canine glioma cell line and in a xenograft glioma model in nude mice. The synergic combination causes mitochondrial membrane depolarization and phosphatidylserine externalization and accelerates death by 48 hours. The lethal process is caspase independent; poly(ADP-ribose) polymerase 1 is not implicated; and there is no apoptosis-inducing factor translocation to the nucleus. The combined system induces autophagic cell death that can be rescued by 3-methyladenine and is characterized by the presence of double-membrane vesicles and punctate LC-3 pattern.
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PMID:Glioma regression in vitro and in vivo by a suicide combined treatment. 1833 48