Thyme Oil & Cancer

Thyme belongs to the Lamiaceae family; due to its wide spectrum of pharmacological properties, it has been used in traditional medicine for thousands of years in countries of the Mediterranean basin. Essential oil of the most studied species, Thyme vulgaris, and its principal component thymol has been shown to have antifungal, antibacterial [1, 2], and antioxidant [3] activities. Therefore, thyme is usually employed as expectorant in upper respiratory tract infection, and thymol is often the main antiseptic ingredient in mouth rinses against gingivitis.

In 2007, Ait M’Barek and colleagues tested the cytotoxic effect of Moroccan endemic thyme (Thymus broussonetii) essential oil in human ovarian adenocarcinoma cell line (IGR-OV1) and its parental cell line resistant to three chemotherapeutic drugs currently used to treat the ovarian adenocarcinoma (adriamycin, vincristine, and cisplatinum) [58]. In this study all cell lines were sensitive to the cytotoxic effects of the essential oil, although they had a different degree of sensitivity reporting an IC50 ranging between 0.39 and 0.94%; importantly, the authors also showed that administration of the essential oil at the tumor site for 30 days in tumor bearing DBA-2 () mice inhibited tumor proliferation, reduced tumor volume, and delayed mouse mortality [4].

In human UMSCC1 head and neck squamous cell carcinoma (HNSCC) cells subtoxic concentrations of Thymus vulgaris essential oil stimulated proliferation and viability, while, at higher concentrations, dose-dependent cytotoxic effects were found [5]; under this experimental setting, the observed cytotoxicity induced by the essential oil was associated, as shown by a microarray-based mRNA expression profiling and pathway analysis, with the regulation of three pathways, namely, the interferon signaling, N-glycan biosynthesis, and ERK5 signaling that could be all involved in the effect of thyme essential oils on cancer cell growth and survival [6]. Interestingly, a recent study testing the cytotoxicity of ten essential oils (mint, ginger, lemon, grapefruit, jasmine, lavender, chamomile, thyme, rose, and cinnamon) identified thyme as the most effective on human prostate carcinoma (PC3), human lung carcinoma (A549), and human breast cancer (MCF7) cell lines [7].

 

1. S. Cosentino, C. I. G. Tuberoso, B. Pisano et al., “In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils,” Letters in Applied Microbiology, vol. 29, no. 2, pp. 130–135, 1999. View at Publisher · View at Google Scholar · View at Scopus


2. D. Kalemba and A. Kunicka, “Antibacterial and antifungal properties of essential oils,” Current Medicinal Chemistry, vol. 10, no. 10, pp. 813–829, 2003. View at Publisher · View at Google Scholar · View at Scopus


3. K. Miura, H. Kikuzaki, and N. Nakatani, “Antioxidant activity of chemical components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.) measured by the oil stability index method,” Journal of Agricultural and Food Chemistry, vol. 50, no. 7, pp. 1845–1851, 2002. View at Publisher · View at Google Scholar · View at Scopus


4. L. Ait M’Barek, H. Ait Mouse, A. Jaâfari et al., “Cytotoxic effect of essential oil of thyme (Thymus broussonettii) on the IGR-OV1 tumor cells resistant to chemotherapy,” Brazilian Journal of Medical and Biological Research, vol. 40, no. 11, pp. 1537–1544, 2007. View at Publisher · View at Google Scholar · View at Scopus


5. S. Sertel, T. Eichhorn, P. K. Plinkert, and T. Efferth, “Cytotoxicity of Thymus vulgaris essential oil towards human oral cavity squamous cell carcinoma,” Anticancer Research, vol. 31, no. 1, pp. 81–87, 2011. View at Google Scholar · View at Scopus


6. Y. Zu, H. Yu, L. Liang et al., “Activities of ten essential oils towards Propionibacterium acnes and PC-3, A-549 and MCF-7 cancer cells,” Molecules, vol. 15, no. 5, pp. 3200–3210, 2010. View at Publisher · View at Google Scholar · View at Scopus

Thyme Oil & Cancer

Bergamot potential application as chemotherapeutic for breast cancer

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