Bergamot essential oil (BEO) is a well-known plant extract, obtained by cold pressing of the epicarp and, partly, of the mesocarp of the fresh fruit of bergamot (Citrus bergamia, Risso et Poiteau). The fruit belongs to the genus Citrus of the Rutaceae family and grows, almost exclusively, in a restricted area along the coast of Southern Italy.
BEO comprises a volatile fraction (93–96% of total) containing monoterpene and sesquiterpene hydrocarbons and oxygenated derivatives and a nonvolatile fraction (4–7% of total) characterized by coumarins and furocoumarins . The most abundant components of the essential oil are the monoterpene hydrocarbon d-limonene and the monoterpene ester, linalyl acetate, with d-limonene accounting for about 40% of the whole oil .
Bergamot essential oil has been used by folk medicine as antiseptic and antihelminthic and to facilitate wound healing and these uses are now supported by experimental data reporting the antifungal and antimicrobial activities of the phytocomplex as well as its ability to increase oxidative metabolism in human polymorphonuclear leukocytes . Recently, analgesic , anxiolytic , and neuroprotective effects have been ascribed to bergamot essential oil and these are consistent with the use of the oil in aromatherapy for the relief of pain and symptoms associated with stress-induced anxiety and depression. Furthermore it has been shown in rodents that BEO affects synaptic transmission by modulating the release of specific amino acid neurotransmitters and it produces a dose-related sequence of sedative and stimulatory behavioral effects in freely moving, normal rats.
Despite the number of studies on the effects of bergamot essential oil under pathological or normal conditions, data regarding its potential activity on tumor cells have only recently been gained. Accordingly, a recent study reported that exposure of human SH-SY5Y neuroblastoma cells to 0.02 and 0.03% bergamot essential oils significantly reduced cell viability inducing both necrotic and apoptotic cell death; cytotoxicity induced by the phytocomplex was accompanied by cytoskeletal alteration, mitochondrial dysfunction, caspase-3 activation, DNA fragmentation, plasma membrane damage, and cleavage of prosurvival proteins. The mixed features of necrotic and apoptotic cell death induced by bergamot essential oil might be related to its complex phytochemical composition, suggesting that different components might activate different pathways to execute cell death. A follow-up study engaged to identify the components responsible for cell death induced by the phytocomplex showed that, at comparable concentrations with those found in cytotoxic concentrations of the oil, none of the tested constituents (d-limonene, linalyl acetate, linalool, -terpinene, -pinene, and bergapten) reduced SH-SY5Y cell viability, while only the combination of limonene and linalyl acetate was able to induce cell death. Accordingly, the bergapten-free fraction of bergamot essential oil was shown to be more effective than the complete phytocomplex suggesting that bergapten is not the main component responsible for the observed cytotoxicity.
Interestingly, it was recently shown that bergamot essential oil and its main component limonene activate autophagy in SH-SY5Y human neuroblastoma and MCF7 human breast cancer cell lines. This effect was concentration-dependent, unrelated to the effects elicited by the essential oil on cell survival, and occurred with a mTOR-independent mechanism. In view of the role of autophagy in limiting cancer development while facilitating advanced tumor progression, the finding that an essential oil is able to activate this pathway can be extremely relevant for its potential application as chemotherapeutic and therefore it stimulates further studies.
As for other essential oils, the hydrophobic nature of bergamot essential oil requires the use of solvents endowed with toxic effects (i.e., DMSO, ethanol) that can limit the therapeutic use of the phytocomplex. Celia and colleagues (2013) recently showed that this limitation could be overcome by loading the essential oil in pegylated liposomes; in addition, the liposomal formulation of bergamot essential oil showed enhanced cytotoxic effect in neuroblastoma cells as compared to the free phytocomplex. Similarly, encapsulation of other essential oils in nanocarriers (i.e., polymeric nanoparticulate formations and lipid carriers, such as liposomes) might represent a good strategy for improving water solubility and stability of essential oils while lowering their effective dose and limiting potential side effects.
Bergamot potential application as chemotherapeutic for breast cancer
No comments:
Post a Comment