title: The effect of antitumor glycosides on glioma cells and tissues as studied by proton HR-MAS NMR spectroscopy.
abstract: The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning ((1)H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the (1)H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death.
authors.affiliation: Unidad de Neurología Experimental, Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha (SESCAM), Toledo, Spain ; Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Álvarez
authors.forename: Leoncio
authors.initials: L
authors.lastname: Garrido
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Romero-Ramírez
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Sampedro
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.forename: Ramón
authors.initials: R
authors.lastname: Campos-Olivas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D013654:Taurine / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D010743:Phospholipids; D013654:Taurine; D002794:Choline