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Depression: 21st Century Solutions + The Dark Side of Wheat

Article Publish Status: FREE
Abstract Title:

Cannabinoids inhibit the vascular endothelial growth factor pathway in gliomas.

Abstract Source:

Cancer Res. 2004 Aug 15 ;64(16):5617-23. PMID: 15313899

Abstract Author(s):

Cristina Blázquez, Luis González-Feria, Luis Alvarez, Amador Haro, M Llanos Casanova, Manuel Guzmán

Article Affiliation:

Cristina Blázquez

Abstract:

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.

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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