Glioma growth inhibition by neurostatin and O-But GD1b.
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 GD1b) 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 are 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.
Valle-Argos
Beatriz
B
Neural Plasticity Group, Functional and Systems Neurobiology Department, Instituto Cajal, Madrid, Spain.
Gómez-Nicola
Diego
D
Nieto-Sampedro
Manuel
M
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005732:Gangliosides; D006028:Glycosphingolipids; C116059:neurostatin; C033851:ganglioside, GD1b