Differentiating and apoptotic dose-dependent effects in (-)-alpha-bisabolol-treated human endothelial cells.
The effect on angiogenesis of (-)-alpha-bisabolol [(-)-6-methyl-2-(4-methyl-3-cyclohexen-1-yl)-5-hepten-2-ol] (1), a widely distributed plant sesquiterpene alcohol, was investigated for the first time. Human endothelial cells treated with 1 were analyzed for their ability to differentiate and organize in microvessels and for their sensitivity to this compound in terms of cytotoxicity and cell growth inhibition. Within 24 h of the treatment with 5 microM 1, cells underwent massive death. Apoptosis induction was responsible for cytotoxicity triggered by 1 as revealed by the release of cytochrome c from the mitochondria, reduction of the Bcl-2/Bax ratio, and caspase 3 activation. At a lower, non-apoptotic concentration (0.25 microM), 1 showed a differentiating effect resulting in growth inhibition, invasiveness reduction, and tubule stabilization.
Magnelli
Lucia
L
Department of Experimental Pathology and Oncology, University of Firenze, Florence, Italy.
Caldini
Riccardo
R
Schiavone
Nicola
N
Suzuki
Hisanori
H
Chevanne
Marta
M
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D000081222:Monocyclic Sesquiterpenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D051028:bcl-2-Associated X Protein / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D000081222:Monocyclic Sesquiterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; C004497:bisabolol; D045304:Cytochromes c