Journal
NEURO-ONCOLOGY
Volume 12, Issue 11, Pages 1135-1146Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noq073
Keywords
C6 cells; gangliosides; glioma; Neurostatin; O-But GD1b
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Funding
- Inocente-Inocente Foundation
- FUHNPAIIN Foundation
- Spanish Department of Ciencia e Innovacion [SAF 2006-11224]
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In spite of their low incidence, central nervous system tumors have elevated morbidity and mortality, being responsible for 2.3% of total cancer deaths. The ganglioside O-acetylated GD1b (O-Ac GD1b neurostatin), present in the mammalian brain, and the semi-synthetic O-butyrylated GD1b (O-But Ga1b) are potent glioma proliferation inhibitors, appearing as possible candidates for the treatment of nervous system tumors. Tumoral cell division inhibitory activity in culture correlated with growth inhibition of glioma xenotransplants in Foxn1(nu) nude mice and intracranial glioma allotransplants. Both O-Ac GD1b and O-But GD1b inhibited in vivo cell proliferation, induced cell cycle arrest, and potentiated immune cell response to the - tumor. Furthermore, the increased stability of the butyrylated compound (O-But GD1b) enhanced its activity with respect to the acetylated ganglioside (neurostatin). These results arc the first report of the antitumoral activity of neurostatin and a neurostatin-like compound in vivo and indicate that semi-synthetic O-acetylated and O-butyrylated gangliosides are potent antitumoral compounds that should be considered in strategies for brain tumor treatment.
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