bisabolol and Breast-Neoplasms

The essential oils from Commiphora species have for centuries been recognized to possess medicinal properties. Here, we performed gas chromatography-mass spectrometry on the essential oil from opoponax (Commiphora guidotti) and identified bisabolene isomers as the main constituents of this essential oil. Opoponax essential oil, a chemical component; β-bisabolene and an alcoholic analogue, α-bisabolol, were tested for their ability to selectively kill breast cancer cells. Only β-bisabolene, a sesquiterpene constituting 5% of the essential oil, exhibited selective cytotoxic activity for mouse cells (IC50 in normal Eph4: >200 µg/ml, MG1361: 65.49 µg/ml, 4T1: 48.99 µg/ml) and human breast cancer cells (IC50 in normal MCF-10A: 114.3 µg/ml, MCF-7: 66.91 µg/ml, MDA-MB-231: 98.39 µg/ml, SKBR3: 70.62 µg/ml and BT474: 74.3 µg/ml). This loss of viability was because of the induction of apoptosis as shown by Annexin V-propidium iodide and caspase-3/7 activity assay. β-bisabolene was also effective in reducing the growth of transplanted 4T1 mammary tumours in vivo (37.5% reduction in volume by endpoint). In summary, we have identified an anti-cancer agent from the essential oil of opoponax that exhibits specific cytotoxicity to both human and murine mammary tumour cells in vitro and in vivo, and this warrants further investigation into the use of β-bisabolene in the treatment of breast cancers.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Caspases; Commiphora; Female; Gas Chromatography-Mass Spectrometry; Humans; MCF-7 Cells; Mice; Monocyclic Sesquiterpenes; Oils, Volatile; Phytotherapy; Plant Extracts; Sesquiterpenes

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.

Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Female; Fibroblasts; Glioma; Humans; Male; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Monocyclic Sesquiterpenes; Neutrophils; Prostatic Neoplasms; Sesquiterpenes; T-Lymphocytes