Inhibition of established subcutaneous murine tumour growth with topical Melaleuca alternifolia (tea tree) oil

Systemic toxicity coupled with long treatment regimes of approved topical chemotherapeutic agents such as imiquimod and 5-fluorouracil (5-FU) are limiting. There is now more focus on the potential use of topical terpene agents as skin cancer treatments. Here, we show for the first time that topical Melaleuca alternifolia (tea tree) oil (TTO), abundant in terpenes, has in vivo antitumour activity. Topical TTO formulations applied to immunocompetent tumour-bearing mice were assessed for antitumour efficacy by monitoring tumour growth and by histological analysis following treatment. Four, daily, topical treatments of 10% TTO/DMSO regressed subcutaneous AE17 mesotheliomas in mice for a period of 10 days and significantly retarded the growth of subcutaneous B16-F10 melanomas. The antitumour effect of topical 10% TTO/DMSO was accompanied by skin irritation similar to other topical chemotherapeutic agents, but unlike other approved topical agents, quickly and completely resolved. Furthermore, we show that topical 10% TTO/DMSO caused an influx of neutrophils and other immune effector cells in the treated area, with no evidence of systemic toxicity. TTO combined with an effective carrier significantly inhibited the growth of aggressive, subcutaneous, chemo-resistant tumours in immunocompetent mice. Taken together, these findings highlight the potential of topical TTO as an alternative topical antitumour treatment.