Inhibition of tumor angiogenesis by cannabinoids.
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.
Blázquez
Cristina
C
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
Casanova
M Llanos
ML
Planas
Anna
A
Gómez Del Pulgar
Teresa
T
Villanueva
Concepción
C
Fernández-Aceñero
María J
MJ
Aragonés
Julián
J
Huffman
John W
JW
Jorcano
José L
JL
Guzmán
Manuel
M
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D042702:Angiopoietin-2; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002186:Cannabinoids / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D042702:Angiopoietin-2; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002186:Cannabinoids; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC