Cannabidiol inhibits angiogenesis by multiple mechanisms

作者：Marcello Solinas, Paola Massi, Anna Rita Cantelmo, Maria Grazia Cattaneo, R. Cammarota, Desirée Bartolini, Valentina Cinquina, Marta Valenti, Lucia Maria Vicentini, Douglas McClain Noonan, Adriana Albini, Daniela Parolaro · 发表于：British Journal of Pharmacology · 年份：2012 · DOI：10.1111/j.1476-5381.2012.02050.x · 被引用次数：170 · 研究领域：Cannabis and Cannabinoid Research、Hippo pathway signaling and YAP/TAZ、Toxin Mechanisms and Immunotoxins

BACKGROUND AND PURPOSE: Several studies have demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on various tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits the growth of different types of tumours in vitro and in vivo and down-regulates some pro-angiogenic signals produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favourable pharmacological and toxicological profile, here, we evaluated the ability of CBD to modulate tumour angiogenesis. EXPERIMENTAL APPROACH: Firstly, we evaluated the effect of CBD on human umbilical vein endothelial cell (HUVEC) proliferation and viability - through [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and FACS analysis - and in vitro motility - both in a classical Boyden chamber test and in a wound-healing assay. We next investigated CBD effects on different angiogenesis-related proteins released by HUVECs, using an angiogenesis array kit and an ELISA directed at MMP2. Then we evaluated its effects on in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels, and further characterized its effects in vivo using a Matrigel sponge model of angiogenesis in C57/BL6 mice. KEY RESULTS: CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion and sprouting in vitro,...