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


CONCLUSIONS
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.
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. demelza.ireland@uwa.edu.au
Demelza J
DJ
Ireland
Sara J
SJ
Greay
Cornelia M
CM
Hooper
Haydn T
HT
Kissick
Pierre
P
Filion
Thomas V
TV
Riley
Manfred W
MW
Beilharz
D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D031650:Melaleuca / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D020947:Tea Tree Oil / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D020947:Tea Tree Oil; D004121:Dimethyl Sulfoxide