Terpinen-4-ol, The Main Component of Melaleuca Alternifolia (Tea Tree) Oil Inhibits the In Vitro Growth of Human Melanoma Cells

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.

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

“…Furthermore, bactericidal (Loughlin et al, 2008) and antifungal properties (Mondello et al, 2006) have also been found in terpinen-4-ol. Moreover, cytotoxicity of terpinen-4-ol on cancer cell lines, e.g., melanoma, has been reported (Calcabrini et al, 2004); which potently induces cell cycle arrest, apoptosis and necrotic cell death (Greay et al, 2010). There is no report of the clinically curative effect of terpinen-4-ol on cancer treatment, but terpinen-4-ol contained anti-inflammatory activity.…”

Biosynthesis and Therapeutic Properties ofLavandulaEssential Oil Constituents

“…Subsequent studies into the chemoprevention potential of perillyl alcohol were undertaken in National Cancer Institute-sponsored phase I, II, and III trials for prostate, breast, and colon cancers. Other lavender oil constituents, such as 1,8-cineole [52] and terpinen-4-ol [53], also display anticancer properties in vitro by inducing apoptosis in tumor cells. Nerolidol, a sesquiterpene found in some lavender essential oils, is also believed to have anticancer potential, as rats fed diets laced with nerolidol showed significantly reduced adenomas and the number of tumors per rat [54].…”

Induction of Intrinsic and Extrinsic Apoptosis Pathways in the Human Leukemic MOLT-4 Cell Line by Terpinen-4-ol

“…Furthermore, it can impair the growth of human M14 melanoma cells (Calcabrini et al, 2004) as well as induces necrotic cell death coupled with apoptotic cell death and arrests cell cycle at G1 stage in mouse malignant mesothelioma AE17 and murine melanoma B16-F10 cells (Greay et al, 2010). Further studies of potential anti-cancer drugs with a variety of cell lines are necessary, because there are high variability responses in different cancer cells following treatment with cytotoxic agents.…”