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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
9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of 9-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.
March 2000 Volume 6 Number 3 pp 313 - 319
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 M Guzmán. e-mail: mgp@solea.quim.ucm.es
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