cytochrome-c-t and bisabolol

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.

Topics: Angiogenesis Inducing Agents; Apoptosis; bcl-2-Associated X Protein; Cytochromes c; Dose-Response Relationship, Drug; Endothelial Cells; Humans; Mitochondria; Monocyclic Sesquiterpenes; Proto-Oncogene Proteins c-bcl-2; Sesquiterpenes; Stereoisomerism

In this study, alpha-bisabolol, a sesquiterpene alcohol present in natural essential oil, was found to have a strong time- and dose-dependent cytotoxic effect on human and rat glioma cells. After 24 h of treatment with 2.5-3.5 microM alpha-bisabolol, the viability of these cells was reduced by 50% with respect to untreated cells. Furthermore, the viability of normal rat glial cells was not affected by treatment with alpha-bisabolol at the same concentrations as above. Glioma cells treated with high concentration of alpha-bisabolol (10 microM) resulted in a 100% cell death. Judging from hypo-G1 accumulation, poly(ADP-ribose) polymerase cleavage, and DNA ladder formation, the cytotoxicity triggered by alpha-bisabolol resulted from apoptosis induction. Moreover, the dissipation of mitochondrial-inner transmembrane potential and the release of cytochrome c from mitochondria indicated that, in these glioma cells, apoptosis occurred through an intrinsic pathway. As pointed out by the experimental results, alpha-bisabolol may be considered a novel compound able to inhibit glioma cell growth and survival.

Topics: Animals; Antineoplastic Agents; Apoptosis; Astrocytes; Cell Line, Tumor; Cell Membrane Permeability; Cell Survival; Cytochromes c; Cytoplasm; Cytosol; DNA Fragmentation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flow Cytometry; Glioma; Humans; Intracellular Membranes; Mitochondria; Monocyclic Sesquiterpenes; Poly(ADP-ribose) Polymerases; Rats; Sesquiterpenes