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)

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.
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PMID:Chemical, metabolic and immunological characterization of gangliosides of human glioma cells. 992 80

Glycosphingolipid GM3, a known suppressor of epidermal growth factor receptor (EGFR) phosphorylation, inhibits cell proliferation. Valproic acid, conversely, is known as an up-regulator of GM3 synthase gene (ST3GAL5). To test the possibility that valproic acid could inhibit EGFR phosphorylation by increasing the level of GM3 in cells, we treated A431 epidermoid carcinoma cells with valproic acid and found that valproic acid treatment caused an about 6-fold increase in the GM3 level but only a marginal increase in the GM2 level in these cells and that the observed increase in GM3 level was valproic acid dose-dependent. Consistent with this observation, valproic acid treatment induced GM3 synthase gene expression by about 8-fold. Furthermore, phosphorylation of EGFR was reduced, and cell proliferation was inhibited following valproic acid treatment. Consistent with these results, transient expression of GM3 synthase gene in A431 cells also increased cellular level of GM3, reduced phosphorylation of EGFR, and inhibited cell proliferation. Treatment with l-phenyl-2-decanoylamino-3-morpholino-l-propanol, an inhibitor of glucosylceramide synthesis, decreased the cellular level of GM3 and reduced the inhibitory effects of valproic acid on EGFR phosphorylation and cell proliferation. These results suggested that induction of GM3 synthesis was enough to inhibit proliferation of cancer cells by suppressing EGFR activity. Valproic acid treatment similarly increased the GM3 level and reduced phosphorylation of EGFR in U87MG glioma cells and inhibited their proliferation. These results suggested that up-regulators of GM3 synthase gene, such as valproic acid, are potential suppressors of cancer cell proliferation.
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PMID:Induction of Glycosphingolipid GM3 Expression by Valproic Acid Suppresses Cancer Cell Growth. 2753 56