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Review

Natural, synthetic and semisynthetic glycolipid inhibitors of glioma growth

, &
Pages 487-497 | Published online: 22 Apr 2005
 

Abstract

Neurostatin, a natural glycosphingolipid inhibitor of astroblast and astrocytoma division, present in mammalian brain, is the modified ganglioside O-acetylated GD1b. It is cytostatic for rat astroblasts, C6 glioma cells and various human astrocytoma lines grades III and IV, with median inhibitory dose values ranging 1 – 5 μM. Neurostatin was shown not to affect primary or transformed fibroblast division at concentrations of ≥ 10 μM. A synthetic neurostatin analogue, NF-115, consisting of an octyl N-acetylglucosaminide derivative with a pentaerythritol chain at position 6, loaded on a slow-delivery polymer disc, caused the destruction of cultured human astroblastoma, obtained after surgical biopsy, and destroyed human neuroectodermic tumours implanted in rats and human astrocytoma implanted in immunodeficient mice. Future antitumourals should combine the high activity of neurostatin with the ease of synthesis of NF-115.

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