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10-20-2012, 01:44 PM
CANNABIDIOL INHIBITS ANGIOGENESIS BY MULTIPLE MECHANISMS.
Solinas M, Massi P, Cantelmo A, Cattaneo M, Cammarota R, Bartolini D, Cinquina V, Valenti M, Vicentini L, Noonan D, Albini A, Parolaro D.
Source
Department of Biomedical, Computer and Communication Sciences, University of Insubria, Busto Arsizio (VA), Italy, Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, 20129 Milan, Italy, Oncology Research Laboratory, Science and Technology Park, IRCCS MultiMedica, 20138 Milan, Italy, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy.
Abstract
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. 2012 The Authors. British Journal of Pharmacology 2012 The British Pharmacological Society.
2012 The Authors. British Journal of Pharmacology 2012 The British Pharmacological Society.
Source: http://www.ncbi.nlm....pubmed/22624859
Solinas M, Massi P, Cantelmo A, Cattaneo M, Cammarota R, Bartolini D, Cinquina V, Valenti M, Vicentini L, Noonan D, Albini A, Parolaro D.
Source
Department of Biomedical, Computer and Communication Sciences, University of Insubria, Busto Arsizio (VA), Italy, Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, 20129 Milan, Italy, Oncology Research Laboratory, Science and Technology Park, IRCCS MultiMedica, 20138 Milan, Italy, Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy.
Abstract
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. 2012 The Authors. British Journal of Pharmacology 2012 The British Pharmacological Society.
2012 The Authors. British Journal of Pharmacology 2012 The British Pharmacological Society.
Source: http://www.ncbi.nlm....pubmed/22624859