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The FASEB Journal Express Article doi:10.1096/fj.02-0795fje
Published online January 2, 2003

Inhibition of tumor angiogenesis by cannabinoids

Cristina Blázquez, M. Llanos Casanova, Anna Planas, Teresa Gómez del Pulgar, Concepción Villanueva, María J. Fernández-Aceñero, Julián Aragonés, John W. Huffman, José L. Jorcano, and Manuel Guzmán

E-mail contact: mgp{at}bbm1.ucm.es

Cannabinoids, the active components of marijuana and their derivatives, induce tumor regression in rodents (8). However, the mechanism of cannabinoid antitumoral action in vivo is as yet unknown. Here we show that local administration of a nonpsychoactive cannabinoid to mice inhibits angiogenesis of malignant gliomas as determined by immunohistochemical analyses and vascular permeability assays. In vitro and in vivo experiments show that at least two mechanisms may be involved in this cannabinoid action: the direct inhibition of vascular endothelial cell migration and survival as well as the decrease of the expression of proangiogenic factors (vascular endothelial growth factor and angiopoietin-2) and matrix metalloproteinase-2 in the tumors. Inhibition of tumor angiogenesis may allow new strategies for the design of cannabinoid-based antitumoral therapies.

Key words: cancer · vascular endothelium · angiogenic factor · apoptosis · experimental therapeutics




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