SUMMARY. Background and purpose: Several studies demonstrated anti-proliferative and pro-apoptotic actions of cannabinoids on several tumours, together with their anti-angiogenic properties. The non-psychoactive cannabinoid cannabidiol (CBD) effectively inhibits in vitro and in vivo the growth of different types of tumours and down-regulates some pro-angiogenic signal produced by glioma cells. As its anti-angiogenic properties have not been thoroughly investigated to date, and given its very favorable pharmacological and toxicological profile, here we evaluated CBD ability to modulate tumour angiogenesis. Experimental approach: We firstly evaluated CBD effect on human umbilical vein endothelial cell (HUVEC) proliferation and viability– through MTT 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 angiogenic Array Kit and an enzyme-linked immunosorbent assay (ELISA) directed at MMP2. Afterwards we evaluated in vitro angiogenesis in treated HUVECs invading a Matrigel layer and in HUVEC spheroids embedded into collagen gels. We further characterized CBD effects using a Matrigel sponge model of in vivo angiogenesis. Key results: CBD induced HUVEC cytostasis without inducing apoptosis, inhibited HUVEC migration, invasion, and sprouting in vitro, and angiogenesis in vivo in matrigel sponges. These effects were associated with down-modulation of several angiogenesis-related molecules. Conclusions and Implications: This study reveals that CBD inhibits angiogenesis by multiple mechanisms. Its dual effect on both tumour and endothelial cells reinforces the hypothesis that CBD could represent a potential effective agent in cancer therapy.
Cannabidiol inhibits angiogenesis by multiple mechanisms / M. Solinas, P. Massi, A.R. Cantelmo, M.G. Cattaneo, R. Cammarota, D. Bartolini, V. Cinquina, M. Valenti, L.M. Vicentini, D.M. Noonan, A. Albini, D. Parolaro. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 167:6(2012 Nov), pp. 1218-1231.
|Titolo:||Cannabidiol inhibits angiogenesis by multiple mechanisms|
MASSI, PAOLA (Secondo)
CATTANEO, MARIA GRAZIA (Primo)
|Parole Chiave:||angiogenesis; cannabidiol; HUVEC; invasion; migration; tube formation|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||nov-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1476-5381.2012.02050.x|
|Appare nelle tipologie:||01 - Articolo su periodico|