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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/49185
Title: Lipid and ganglioside alterations in tumor cells treated with antimitotic oleyl glycoside
Authors: García Álvarez, Isabel; Egido-Gabás, Meritxell; Romero-Ramírez, Lorenzo; Doncel-Pérez, Ernesto; Nieto-Sampedro, Manuel; Casas, Josefina; Fernández-Mayoralas, Alfonso
Issue Date: 2011
Publisher: Royal Society of Chemistry (Great Britain)
Citation: Molecular BioSystems
Abstract: Oleyl 2-acetamido-2-deoxy-α-D-glucopyranoside (1) was previously shown to exhibit antimitotic activity on glioma (C6) and melanoma (A375) cell lines. Preliminary studies about its mechanism of action using 1H MAS NMR suggested that 1 may be altering the metabolism of lipids. We have now studied the effect of 1 on the fatty acid, sphingolipid and ganglioside content in a line of carcinomic human alveolar epithelial cells (A549) using UPLC-MS. Oleic acid and NB-DNJ were used as positive controls for inhibition of fatty acid and ganglioside synthesis, respectively. Compound 1 (10 μM) was more efficient than oleic acid in reducing fatty acid levels of A549 cells, producing a decrease in the range of 40–15%, depending on the acyl chain length and the number of insaturations. In addition, glycoside 1 caused a reduction on ganglioside content of A549 tumor cell line and accumulation of lactosylceramide, the common metabolic precursor for ganglioside biosynthesis. Alteration of ganglioside metabolism was also observed with two galactosylated derivatives of 1, which caused a more pronounced increase in lactosylceramide levels. Compound 1 at higher concentrations (above 30 μM) produced drastic alterations in glycosphingolipid metabolism, leading to cell metabolic profiles very different from those obtained at 10 μM. These biochemical changes were ascribed to activation of endoplasmic reticulum stress pathways.
Publisher version (URL): http://dx.doi.org/10.1039/C0MB00125B
URI: http://hdl.handle.net/10261/49185
DOI: 10.1039/C0MB00125B
ISSN: 1742-206X
E-ISSN: 1742-2051
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