Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells

J Invest Dermatol. 2004 Feb;122(2):349-60. doi: 10.1046/j.0022-202X.2004.22236.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / ultrastructure
  • Cell Membrane / ultrastructure
  • Drug Resistance, Neoplasm
  • Freeze Fracturing
  • Humans
  • In Vitro Techniques
  • Melaleuca*
  • Melanoma*
  • Microscopy, Electron, Scanning
  • Skin Neoplasms*
  • Tea Tree Oil / pharmacology*
  • Terpenes / pharmacology*


  • Anti-Infective Agents
  • Antineoplastic Agents
  • Terpenes
  • terpinenol-4
  • Tea Tree Oil