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

FEBS J. 2009 Aug;276(15):3990-4000. doi: 10.1111/j.1742-4658.2009.07108.x. Epub 2009 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Glioma
  • Humans
  • Male
  • Mitochondrial Membrane Transport Proteins / drug effects
  • Mitochondrial Membrane Transport Proteins / physiology*
  • Mitochondrial Permeability Transition Pore
  • Monocyclic Sesquiterpenes
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Prostatic Neoplasms
  • Sesquiterpenes / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology


  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Monocyclic Sesquiterpenes
  • Sesquiterpenes
  • bisabolol