Interaction of Tea Tree Oil with Model and Cellular Membranes

Abstract

Tea tree oil (TTO) is the essential oil steam-distilled from Melaleuca alternifolia, a species of northern New South Wales, Australia. It exhibits a broad-spectrum antimicrobial activity and an antifungal activity. Only recently has TTO been shown to inhibit the in vitro growth of multidrug resistant (MDR) human melanoma cells. It has been suggested that the effect of TTO on tumor cells could be mediated by its interaction with the plasma membrane, most likely by inducing a reorganization of lipid architecture. In this paper we report biophysical and structural results obtained using simplified planar model membranes (Langmuir films) mimicking lipid "rafts". We also used flow cytometry analysis (FCA) and freeze-fracturing transmission electron microscopy to investigate the effects of TTO on actual MDR melanoma cell membranes. Thermodynamic (compression isotherms and adsorption kinetics) and structural (Brewster angle microscopy) investigation of the lipid monolayers clearly indicates that TTO interacts preferentially with the less ordered DPPC "sea" and that it does not alter the more ordered lipid "rafts". Structural observations, performed by freeze fracturing, confirm that TTO interacts with the MDR melanoma cell plasma membrane. Moreover, experiments performed by FCA demonstrate that TTO does not interfere with the function of the MDR drug transporter P-gp. We therefore propose that the effect exerted on MDR melanoma cells is mediated by the interaction with the fluid DPPC phase, rather than with the more organized "rafts" and that this interaction preferentially influences the ATP-independent antiapoptotic activity of P-gp likely localized outside "rafts".

A review of applications of tea tree oil in dermatology

“…It has been proposed that the effect of TTO on tumor cells is mediated by its induction of a reorganization of the lipid architecture of plasma membrane . Topical 10% TTO/dimethyl sulfoxide (DMSO) has been shown to significantly retard the growth of subcutaneous melanomas .…”

Effects of Mentha suaveolens Essential Oil Alone or in Combination with Other Drugs in Candida albicans

“…Moreover, Giordani et al [34] demonstrated the perturbation of molecular architecture of the plasma membrane of human cancer cell lines, without completely disrupting it, using TTO and terpinen-4-ol. Accordingly, the antimicrobic effect of terpinen4-ol may be due to perturbation of the lipidic fraction of microorganism plasmic membrane, resulting in alterations of membrane properties.…”

Biodegradable Nanoparticles Obtained From Zein as a Drug Delivery System for Terpinen-4-Ol

“…Terpinen-4-ol (T4OL), which is the main component of tea tree oil and is also present in various essential oils (e.g., juniper oil, lavender oil, rosemary oil, majoram oil, and thyme oil), 3 exhibits an in vitro inhibitory effect on the growth of multidrug-resistant human melanoma cells. 4,5 Polymers suitable for use in skin drug delivery systems need to be stable, nonreactive with the drug, inexpensive, and easily manufactured. 6 The zein storage proteins are frequently found in maize endosperm, where they are deposited as protein bodies within the rough endoplasmic reticulum.…”