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Article
Nature Medicine  6, 313 - 319 (2000)
doi:10.1038/73171

Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

Ismael Galve-Roperh1, 3, Cristina Sánchez1, 3, María Luisa Cortés2, Teresa Gómez del Pulgar1, Marta Izquierdo2 & Manuel Guzmán1

1  Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040-Madrid , Spain

2  Department of Molecular Biology, Severo Ochoa Molecular Biology Center, School of Sciences, Autónoma University, 28049-Madrid, Spain

3  I.G.-R. and C.S. contributed equally to this work

Correspondence should be addressed to Manuel Guzmán mgp@solea.quim.ucm.es
Delta9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of Delta9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two subclones of C6 glioma cells in culture showed that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained ceramide accumulation and Raf1/extracellular signal-regulated kinase activation. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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