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Tea tree oil is an essential oil distilled from the leaves of Melaleucaalternifolia, a plant native to Australia. It has been used intraditional medicine for its antiseptic and anti-inflammatory properties totreat various skin conditions and infections. It has also been incorporated intomany topical formulations to treat cutaneous infections and speed wound healing.In vivo and in vitro studies report antiproliferative effectsin skin disorders but the molecular mechanisms underlying this effect remain tobe still elucidated. In this study MTT assay, scanning electron microscopy-fieldemission gun, flow cytometry, cell cycle assays, and laser scanning confocalmicroscopy were utilized to investigate a novel mechanism underlying theantiproliferative effects of tea tree oil and terpinen-4-ol on transformed skin(melanoma) M14 cells. The analysis of the actin cytoskeleton by laser scanningconfocal microscopy evidenced a clear action of both essential oil and its mainactive component on F-actin, which interfered with bundling of actinmicrofilaments in stress fibers. As for the microtubular network, both tea treeoil and terpinen-4-ol induced a disorganization of the perinuclear cage with therupture and collapse of microtubules. Finally, they noticeably changed theintermediate filaments architecture by inducing the formation of large vimentincables. Results obtained in the present study point to the cytoskeleton as afurther target of tea tree oil and terpinen-4-ol and could account for theinhibition of proliferation and invasion of skin transformed M14 cells. In ourexperimental conditions, vimentin intermediate filaments appear to be thecytoskeletal element more affected by the treatments. Moreover, the role ofcross-linker proteins in the mechanism of action of tea tree oil has beendiscussed.

Tea Tree Oil and Terpinen-4-Ol Induce Cytoskeletal Reorganization of Human Melanoma Cells