title: 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".
authors.affiliation: Dipartimento di Tecnologie e Salute, Istituto Superiore di Sanita', Viale Regina Elena 299, 00161 Roma, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Giordani
authors.forename: Agnese
authors.initials: A
authors.lastname: Molinari
authors.forename: Laura
authors.initials: L
authors.lastname: Toccacieli
authors.forename: Annarica
authors.initials: A
authors.lastname: Calcabrini
authors.forename: Annarita
authors.initials: A
authors.lastname: Stringaro
authors.forename: Pietro
authors.initials: P
authors.lastname: Chistolini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Arancia
authors.forename: Marco
authors.initials: M
authors.lastname: Diociaiuti
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000327:Adsorption; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D002784:Cholesterol / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005614:Freeze Fracturing; D005677:G(M1) Ganglioside / Q000737:chemistry; D006801:Humans; D008545:Melanoma; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects; D008567:Membranes, Artificial; D046529:Microscopy, Electron, Transmission; D020947:Tea Tree Oil / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D008567:Membranes, Artificial; D015060:1,2-Dipalmitoylphosphatidylcholine; D005677:G(M1) Ganglioside; D020947:Tea Tree Oil; D002784:Cholesterol