期刊
FEBS JOURNAL
卷 276, 期 15, 页码 3990-4000出版社
WILEY
DOI: 10.1111/j.1742-4658.2009.07108.x
关键词
alpha-bisabolol; apoptosis; cyclosporine A; mitochondria; mitochondrial permeability transition pore
资金
- Italian Ministry of University and Scientific and research [COFIN2002]
- CARIVERONA
alpha-Bisabolol is a natural monocyclic sesquiterpene alcohol. It has been used in cosmetics for hundreds of years because of its perceived skin-healing properties. alpha-Bisabolol is known to have anti-irritant, anti-inflammatory and antimicrobial properties. In precedent studies, we described how alpha-bisabolol exerts a selective pro-apoptotic action towards transformed cells [Cavalieri E et al. (2004) Biochem Biophys Res Commun315, 589-594] and its uptake is mediated by lipid rafts on the plasma membrane [Darra E et al. (2008) Arch Biochem Biophys476, 113-123]. In this study, we hypothesize that the intracellular target of alpha-bisabolol may be the mitochondrial permeability transition pore (mPTP). To evaluate this hypothesis, we used one transformed cell line (human glioma T67) in comparison with a nontransformed one (human fibroblasts). We assessed the effect of a specific mPTP inhibitor (cyclosporine A) on the toxic action of alpha-bisabolol. Results show that the alpha-bisabolol-induced decrease in oxygen consumption is abolished by the addition of cyclosporine A in T67 cells, indicating that alpha-bisabolol may target mPTP. The central role of mitochondria was also demonstrated by using galactose to force cells to a more aerobic metabolism. In this condition, we observed higher alpha-bisabolol toxicity. Furthermore, we studied the effect of alpha-bisabolol on isolated rat liver mitochondria. This study expands the notion of the specific action of alpha-bisabolol on transformed cells and suggests that it may act by disturbing the structure and function of the mPTP. alpha-Bisabolol toxicity is clearly related to its cellular uptake, which is higher in transformed cell lines.
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