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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Article info
Publication history
Published online: June 25, 2012
Accepted:
May 21,
2012
Received in revised form:
April 13,
2012
Received:
November 2,
2011
Identification
Copyright
© 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.