1. Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy
2. ^*Laboratorio di Tossicologia Comparata ed Ecotossicologia, Istituto Superiore di Sanità, Rome, Italy
3. ^†Laboratorio di Batteriologia e Micologia Medica, Istituto Superiore di Sanità, Rome, Italy

Correspondence: Agnese Molinari, Laboratorio di Ultrastrutture, Istituto Superiore di Sanità Viale Regina Elena 299, 00161 Rome, Italy. Email: molinari@iss.it

Received 20 August 2002; Revised 30 September 2003; Accepted 1 October 2003; Published online 12 February 2004.

Abstract

The search for innovative therapeutic approaches based on the use of new substances is gaining more interest in clinical oncology. In this in vitro study the potential anti-tumoral activity of tea tree oil, distilled from Melaleuca alternifolia, was analyzed against human melanoma M14 WT cells and their drug-resistant counterparts, M14 adriamicin-resistant cells. Both sensitive and resistant cells were grown in the presence of tea tree oil at concentrations ranging from 0.005 to 0.03%. Both the complex oil (tea tree oil) and its main active component terpinen-4-ol were able to induce caspase-dependent apoptosis of melanoma cells and this effect was more evident in the resistant variant cell population. Freeze-fracturing and scanning electron microscopy analyses suggested that the effect of the crude oil and of the terpinen-4-ol was mediated by their interaction with plasma membrane and subsequent reorganization of membrane lipids. In conclusion, tea tree oil and terpinen-4-ol are able to impair the growth of human M14 melanoma cells and appear to be more effective on their resistant variants, which express high levels of P-glycoprotein in the plasma membrane, overcoming resistance to caspase-dependent apoptosis exerted by P-glycoprotein-positive tumor cells.