Efficacy and action of topical diterpenes from Euphorbia Peplus in non-melanoma skin cancer

Jones, Brad. (2003). Efficacy and action of topical diterpenes from Euphorbia Peplus in non-melanoma skin cancer MPhil Thesis, School of Medicine, The University of Queensland.

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Author Jones, Brad.
Thesis Title Efficacy and action of topical diterpenes from Euphorbia Peplus in non-melanoma skin cancer
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2003
Thesis type MPhil Thesis
Supervisor A/Prof Peter Parsons
Dr David Whiteman
Total pages 127
Language eng
Subjects 11 Medical and Health Sciences
Formatted abstract
Non-melanoma skin cancer (NMSC) is very prevalent in the general population in Australia and causes considerable morbidity. At present there are several treatment modalities used to treat NMSC including topical medical therapy, radiotherapy, surgery and physical ablative methods. The milky sap of the plant Euphorbia peplus (E. peplus) has long been used as a home remedy for the treatment of skin cancer and the active compounds from the Euphorbiaceae family of plants have been determined to be diterpene esters. These esters were cytotoxic against a variety of cancers both in vivo and in vitro and are the subject of ongoing research around the world.

This thesis examined one of the active diterpene esters from E. peplus called 3- angelyl ingenol (PEP005). The efficacy of PEP005 on murine skin cancer models was evaluated and a hypothesis as to its mode of action was developed. The studies showed that 3 once-daily topical doses of PEP005 (18 µg or less per dose) in an isopropanol gel vehicle was capable of inducing cure in the majority of tumours in the nude mouse models and to a lesser extent the C57BL mouse model. A concentration of 1 mg/ml was an effective topical dose that was well tolerated and 3 once-daily doses were more efficacious than a single high dose or smaller doses applied once-daily for 7 days.

The nature of the inflammatory response following topical PEP005 application was mostly a polymorphonuclear cell infiltration, which appears to be required, to some extent, for its efficacy. Electron microscopy showed the nature of cell death in vivo to be necrosis following mitochondrial swelling. Several inflammatory cytokine and chemokine mRNAs were induced following topical application of PEP005 as determined by semi-quantitative polymerase chain reactions (RT-PCR). Microarray analysis indicated the possible involvement of several interesting genes including those involved in neutrophil chemotaxis and some that modulate the oxidative stress response. These molecular changes will need to be clarified at the protein level.

It is hypothesized that PEP005 has a direct cytotoxic effect on tumour cells and causes this effect via reactive oxygen species (ROS) resulting in disruption to membrane integrity inside the cell. These ROS could be released from the mitochondria of the tumour cells, from the infiltrating neutrophils, or a combination of both. Further research is needed to see whether there is an oxidative stress response of tumour cells exposed to PEP005 compound and to look at these mechanisms and pathways in closer detail.
Keyword Euphorbiaceae
Skin cancer -- Treatment

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
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Created: Tue, 28 Jun 2011, 16:00:06 EST by Eric Sun on behalf of Social Sciences and Humanities Library Service