Differentiating and Apoptotic Dose-Dependent Effects in (−)-α-Bisabolol-Treated Human Endothelial Cells

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2010-04, Vol.73 (4), p.523-526
• Main Authors: Magnelli, Lucia, Caldini, Riccardo, Schiavone, Nicola, Suzuki, Hisanori, Chevanne, Marta
• Format: Article
• Language: English
• Subjects: Angiogenesis Inducing Agents - pharmacology; Apoptosis - drug effects; bcl-2-Associated X Protein - drug effects; Biological and medical sciences; Cytochromes c - drug effects; Cytochromes c - metabolism; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelial Cells - metabolism; General pharmacology; Humans; Medical sciences; Mitochondria - enzymology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Proto-Oncogene Proteins c-bcl-2 - drug effects; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Stereoisomerism
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np9003933

The effect on angiogenesis of (−)-α-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 μM 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 μM), 1 showed a differentiating effect resulting in growth inhibition, invasiveness reduction, and tubule stabilization.