J. Med. Chem., 2009, 52 (5), pp 1263–1267

Detection of Metabolite Changes in C6 Glioma Cells Cultured with Antimitotic Oleyl Glycoside by 1H MAS NMR

Isabel Garca-lvarez, Leoncio Garrido, Ernesto Doncel-Prez, Manuel Nieto-Sampedro and Alfonso Fernndez-Mayoralas

Abstract
The synthetic glycoside, oleyl N-acetyl-α-d-glucosaminide (1), was previously shown to exhibit antimitotic activity on rat (C6) and human (U-373) glioma lines. To obtain information about its mechanism of action, metabolite changes in C6 glioma cells were analyzed after treatment with 1 using high-resolution magic angle spinning 1H NMR. Compound 1 caused either a decrease or an increase in the intensity of the signal assigned to coenzyme A (CoA) metabolites depending on the concentration used. The data obtained from the 1H NMR spectra of cells cultured with 1, combined with those obtained after treatment with oleic acid (an inhibitor of acetyl-CoA carboxylase) and phenyl butyrate (a known antineoplastic agent), suggest that 1 may be altering the metabolism of fatty acids and induce apoptosis of C6 glioma cells. These results point to NMR spectroscopy as an efficient technique for monitoring the response of the cells to therapeutic agents.