Abstract
Tea tree oil is an essential oil distilled from the leaves of Melaleuca
alternifolia, a plant native to Australia. It has been used in
traditional medicine for its antiseptic and anti-inflammatory properties to
treat various skin conditions and infections. It has also been incorporated into
many topical formulations to treat cutaneous infections and speed wound healing.
In vivo and in vitro studies report antiproliferative effects
in skin disorders but the molecular mechanisms underlying this effect remain to
be still elucidated. In this study MTT assay, scanning electron microscopy-field
emission gun, flow cytometry, cell cycle assays, and laser scanning confocal
microscopy were utilized to investigate a novel mechanism underlying the
antiproliferative effects of tea tree oil and terpinen-4-ol on transformed skin
(melanoma) M14 cells. The analysis of the actin cytoskeleton by laser scanning
confocal microscopy evidenced a clear action of both essential oil and its main
active component on F-actin, which interfered with bundling of actin
microfilaments in stress fibers. As for the microtubular network, both tea tree
oil and terpinen-4-ol induced a disorganization of the perinuclear cage with the
rupture and collapse of microtubules. Finally, they noticeably changed the
intermediate filaments architecture by inducing the formation of large vimentin
cables. Results obtained in the present study point to the cytoskeleton as a
further target of tea tree oil and terpinen-4-ol and could account for the
inhibition of proliferation and invasion of skin transformed M14 cells. In our
experimental conditions, vimentin intermediate filaments appear to be the
cytoskeletal element more affected by the treatments. Moreover, the role of
cross-linker proteins in the mechanism of action of tea tree oil has been
discussed.
Key words
Melaleuca alternifolia
- Myrtaceae - tea tree oil - terpinen-4-ol - cytoskeleton - melanoma
