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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
Department of Biochemistry and Molecular Biology I, School of
Biology, Complutense University, Madrid, Spain [CB, MLC, TGDP, JLJ, MG];
Project on Cellular and Molecular Biology and Gene Therapy, CIEMAT, Madrid,
Spain [MLC, JLJ]; Department of Pharmacology and Toxicology, IIBB-CSIC, IDIBAPS,
Barcelona, Spain [AP]; Department of Pathology, Hospital General de Móstoles,
Madrid, Spain [CV, MJF-A]; Department of Immunology, Hospital de la Princesa,
Madrid, Spain [JA]; and Department of Chemistry, Clemson University, Clemson,
South Carolina, USA [JWH].
Correspondence [MG]: Department of Biochemistry and Molecular Biology I, School
of Biology, Complutense University, 28040 Madrid, Spain. E-mail: mgp@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
© 2003 FASEB
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