Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Natural products historically represent a source of clinically approved drugs that have contributed significantly to anticancer drug development. Melaleuca alternifolia Concentration (MAC) is an extract prepared from the native Australian plant M. alternifolia (also a common source of Tea Tree Oil). Initial investigations analysing the in vitro cytotoxicity of Melaleuca oils and its main components against tumour cells revealed the presence of compounds with strong anticancer activities. In vitro, MAC induced cell death through the intrinsic mitochondrial pathway, while at lower cytostatic concentrations induced autophagy and cell cycle arrest in G1 phase. In vivo, the anticancer properties of MAC were examined using a spontaneous FVB/N c-neu murine model of breast cancer, with mice receiving intratumoural treatments every 3 days. MAC suppressed tumour growth over a 30 day period and induction of cell death through the intrinsic mitochondrial pathway was also replicated in vivo, as determined by the presence of both intramitochondrial superoxide and TUNEL positive regions within MAC treated tumours. Potential immunomodulatory activity of MAC was examined in the 4T1 breast cancer model. MAC was associated with increased CD3⁺CD4⁺ and CD3⁺CD8⁺ T cell populations as well as a reduction in CD3⁺CD4⁺CD25⁺Foxp3⁺ regulatory T cells in both tumour and blood. Furthermore, there was an increased presence of Ly6G^hiCD11b⁺ neutrophils in treated tumours and bone marrow. Intratumourally, MAC also elevated the expression of CD80 on Ly6G^hiCD11b⁺ cells, indicating the presence of a potential antigen presenting-type neutrophil population. In both models, MAC treatment was not associated with any observable adverse effects. In conclusion, MAC represents a promising anticancer agent through its ability to induce apoptosis via the intrinsic mitochondrial pathway as well as by reducing tumour growth and promoting an anti-tumour immune response in mice with no observable adverse effects. Additionally, the immunostimulatory response may also aid in combating the prevalence of metastasis due to the increased immune cell presence.