Involvement of mitochondrial permeability transition pore opening in alpha-bisabolol induced apoptosis.

α-Bisabolol is a natural monocyclic sesquiterpene alcohol. It has been used in cosmetics for hundreds of years because of its perceived skin-healing properties. α-Bisabolol is known to have anti-irritant, anti-inflammatory and antimicrobial properties. In precedent studies, we described how α-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 α-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 α-bisabolol. Results show that the α-bisabolol-induced decrease in oxygen consumption is abolished by the addition of cyclosporine A in T67 cells, indicating that α-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 α-bisabolol toxicity. Furthermore, we studied the effect of α-bisabolol on isolated rat liver mitochondria. This study expands the notion of the specific action of α-bisabolol on transformed cells and suggests that it may act by disturbing the structure and function of the mPTP. α-Bisabolol toxicity is clearly related to its cellular uptake, which is higher in transformed cell lines.