Involvement of mitochondrial permeability transition pore opening in alpha-bisabolol induced apoptosis.
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 Commun 315, 589-594] and its uptake is mediated by lipid rafts on the plasma membrane [Darra E et al. (2008) Arch Biochem Biophys 476, 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.
Cavalieri
Elisabetta
E
Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Italy.
Bergamini
Christian
C
Mariotto
Sofia
S
Leoni
Serena
S
Perbellini
Luigi
L
Darra
Elena
E
Suzuki
Hisanori
H
Fato
Romana
R
Lenaz
Giorgio
G
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005910:Glioma; D006801:Humans; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D000081222:Monocyclic Sesquiterpenes; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D011471:Prostatic Neoplasms; D012717:Sesquiterpenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000081222:Monocyclic Sesquiterpenes; D012717:Sesquiterpenes; C004497:bisabolol