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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
Abstract
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.
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