Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models
Open Access
- 31 May 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death Discovery
- Vol. 7 (1), 1-13
- https://doi.org/10.1038/s41420-021-00510-3
Abstract
Essential oils (EOs) have been recently emerging for their promising biological activities in preventing tumorigenesis or progression of different tumor histotypes, including melanoma. In this study, we investigated the antitumor activity of a panel of EOs in different tumor models. The ability of Melaleuca alternifolia (tea tree oil) and its main component, terpinen-4-ol, to sensitize the target therapy currently used for melanoma treatment was also assessed. Our results demonstrated that EOs differently affect the viability of human cancer cells and led us to select six EOs effective in melanoma and lung cancer cells, without toxic effects in human fibroblasts. When combined with dabrafenib and/or trametinib, Melaleuca alternifolia synergistically reduced the viability of melanoma cells by activating apoptosis. Through machine learning classification modeling, α-terpineol, tepinolene, and terpinen-4-ol, three components of Melaleuca alternifolia, were identified as the most likely relevant components responsible for the EO’s antitumor effect. Among them, terpinen-4-ol was recognized as the Melaleuca alternifolia component responsible for its antitumor and proapoptotic activity. Overall, our study holds promise for further analysis of EOs as new anticancer agents and supports the rationale for their use to improve target therapy response in melanoma.Keywords
Funding Information
- IRCCS Regina Elena National Cancer Institute
- Sapienza Università di Roma (Ateneo Grant 2019- P.I. RR (prot. RM11916B8876093E), Ateneo Grant 2018-P.I. RR (prot. RM118164361B425B))
- Associazione Italiana per la Ricerca sul Cancro (IG 2020 - ID. 24315)
This publication has 80 references indexed in Scilit:
- Essential oils fromSchinus terebinthifoliusleaves – chemical composition andin vitrocytotoxicity evaluationPharmaceutical Biology, 2012
- Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In VivoEvidence-Based Complementary and Alternative Medicine, 2012
- Tea Tree Oil Might Combat MelanomaPlanta Medica, 2010
- Activities of Ten Essential Oils towards Propionibacterium acnes and PC-3, A-549 and MCF-7 Cancer CellsMolecules, 2010
- β-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosisOncology Reports, 2009
- Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cellsCell Proliferation, 2008
- Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomasSurgical Neurology, 2008
- Interaction of Tea Tree Oil with Model and Cellular MembranesJournal of Medicinal Chemistry, 2006
- Terpinen-4-ol, The Main Component of Melaleuca Alternifolia (Tea Tree) Oil Inhibits the In Vitro Growth of Human Melanoma CellsJournal of Investigative Dermatology, 2004
- Mutations of the BRAF gene in human cancerNature, 2002