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Research Article| Volume 67, ISSUE 2, P120-129, August 2012

Topically applied Melaleuca alternifolia (tea tree) oil causes direct anti-cancer cytotoxicity in subcutaneous tumour bearing mice

  • Author Footnotes
    1 D.J. Ireland and S.J. Greay contributed equally to this research.
    Demelza J. Ireland
    Correspondence
    Corresponding author. Tel.: +61 8 9346 2214; fax: +61 8 9346 2912.
    Footnotes
    1 D.J. Ireland and S.J. Greay contributed equally to this research.
    Affiliations
    School of Pathology and Laboratory Medicine (M504), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
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  • Author Footnotes
    1 D.J. Ireland and S.J. Greay contributed equally to this research.
    Sara J. Greay
    Footnotes
    1 D.J. Ireland and S.J. Greay contributed equally to this research.
    Affiliations
    School of Pathology and Laboratory Medicine (M504), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
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  • Cornelia M. Hooper
    Affiliations
    School of Pathology and Laboratory Medicine (M504), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
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  • Haydn T. Kissick
    Affiliations
    Department of Surgery, Beth Israel Deaconess Medical Centre, Harvard Medical School, Boston, MA, USA
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  • Pierre Filion
    Affiliations
    Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia
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  • Thomas V. Riley
    Affiliations
    School of Pathology and Laboratory Medicine (M504), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia

    Microbiology and Infectious Diseases, PathWest Laboratory Medicine WA, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia
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  • Manfred W. Beilharz
    Affiliations
    School of Pathology and Laboratory Medicine (M504), Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia
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  • Author Footnotes
    1 D.J. Ireland and S.J. Greay contributed equally to this research.

      Abstract

      Background

      Melaleuca alternifolia (tea tree) oil (TTO) applied topically in a dilute (10%) dimethyl sulphoxide (DMSO) formulation exerts a rapid anti-cancer effect after a short treatment protocol. Tumour clearance is associated with skin irritation mediated by neutrophils which quickly and completely resolves upon treatment cessation.

      Objective

      To examine the mechanism of action underlying the anti-cancer activity of TTO.

      Methods

      Immune cell changes in subcutaneous tumour bearing mice in response to topically applied TTO treatments were assessed by flow cytometry and immunohistochemistry. Direct cytotoxicity of TTO on tumour cells in vivo was assessed by transmission electron microscopy.

      Results

      Neutrophils accumulate in the skin following topical 10% TTO/DMSO treatment but are not required for tumour clearance as neutrophil depletion did not abrogate the anti-cancer effect. Topically applied 10% TTO/DMSO, but not neat TTO, induces an accumulation and activation of dendritic cells and an accumulation of T cells. Although topical application of 10% TTO/DMSO appears to activate an immune response, anti-tumour efficacy is mediated by a direct effect on tumour cells in vivo. The direct cytotoxicity of TTO in vivo appears to be associated with TTO penetration.

      Conclusion

      Future studies should focus on enhancing the direct cytotoxicity of TTO by increasing penetration through skin to achieve a higher in situ terpene concentration. This coupled with boosting a more specific anti-tumour immune response will likely result in long term clearance of tumours.

      Keywords

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