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Cannabinoids inhibit the vascular endothelial growth factor
pathway in gliomas
Blazquez C, Gonzalez-Feria L, Alvarez L, Haro A, Casanova ML, Guzman M
Department of Biochemistry and Molecular Biology I, School of Biology,
Complutense University, Madrid, Spain.
Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their
antiangiogenic action is still unknown.
Because the vascular endothelial growth
factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we
studied whether cannabinoids affect it.
As a first approach, cDNA array analysis
showed that cannabinoid administration to mice bearing s.c. gliomas lowered the
expression of various VEGF pathway-related genes.
The use of other methods
(ELISA, Western blotting, and confocal microscopy) provided additional evidence
that cannabinoids depressed the VEGF pathway by decreasing the production of
VEGF and the activation of VEGF receptor (VEGFR)-2, the most prominent VEGF
receptor, in cultured glioma cells and in mouse gliomas.
Cannabinoid-induced
inhibition of VEGF production and VEGFR-2 activation was abrogated both in vitro
and in vivo by pharmacological blockade of ceramide biosynthesis.
These changes
in the VEGF pathway were paralleled by changes in tumor size.
Moreover,
intratumoral administration of the cannabinoid Delta9-tetrahydrocannabinol to
two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF
levels and VEGFR-2 activation in the tumors.
Because blockade of the VEGF
pathway constitutes one of the most promising antitumoral approaches currently
available, the present findings provide a novel pharmacological target for
cannabinoid-based therapies.
PMID: 15313899 [PubMed - in process]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15313899
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