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

 -  Journal of Natural Products, 73(4), p.523-526, 2010 .
<br/><br/> The effect on angiogenesis of (-)-R-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 ìM 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 ìM), 1 showed a differentiating effect resulting in growth inhibition, invasiveness reduction, and tubule stabilization.