Evaluation of the Anticancer Potential of Plants Used as Traditional Medicines by Aboriginal People
Evaluation of the Anticancer Potential of Plants Used as Traditional Medicines by Aboriginal People Thesis
School of Biological, Biomolecular and Chemical Sciences, Discipline of Physiology
- Author(s): Savigni, Donna
- Published: 2010
- Publisher: University of Western Australia
- Volume: PhD
Abstract: Chapter 1. Aboriginal Australians maintain the oldest continuous culture on earth, and their wealth of phytochemical knowledge is largely unknown to the Western world. This study sought to tap into that knowledge, not only in the hope of finding a compound that may be of therapeutic use to cancer patients outside the indigenous communities, but also to empower the communities themselves. This introductory chapter encompasses why it is important to find new compounds to combat cancer and the various strategies employed to do so. The importance of natural products in current chemotherapies is emphasised. Advantages of the ethnopharmacological approach to screening plants for bioactive compounds are highlighted, leading into a rationale for the current project. Chapter 2. This chapter described the various materials and methods employed in the investigations. Chapter 3. The study began by justifying the choice of cell lines and optimising their culture conditions. Next, the validity of the MTT assay as a measure of cytotoxicity was demonstrated and its refinement was described. Finally, relevant controls for these bioassays were determined. Chapter 4. This chapter examined the ethnopharmacological approach to drug discovery, whereby plants potentially containing suitable drug candidates were selected based on traditional medical knowledge of two Aboriginal desert communities. These plants were screened for bioactivity against a panel of cell lines representative of the five most common types of cancer. Bioactivity was determined by demonstrating a reduction in cancer cell proliferation via the MTT assay. Using this assay, it was shown that more than half of the methanolic extracts of plants identified as having medicinal properties displayed cytotoxic or cytostatic effects against human cancer cell lines. Some of these plant extracts were more potent than others and showed selectivity for different cancer cell types. Chapter 5. From these initial screening studies, four different species were chosen for further evaluation. These were Euphorbia drummondii, Eremophila sturtii, Eremophila duttonii and Acacia tetragonophylla. Fresh specimens of these were collected and fractionated into methanolic, ethyl acetate and aqueous extracts, which also demonstrated a range of cytotoxic and cytostatic effects on cancer cells. The cytotoxicity of several of these extracts appeared to be via a specific mechanism, as opposed to non-specific general toxicity, as brine shrimp were not sensitive to the same treatment. Additionally, the chemical profiles of the various extracts were compared via HPLC and GC-MS analyses. Chapter 6. Based on the results of Chapter 5, the most promising extract, the ethyl acetate extract of E. duttonii (EA3), was chosen for characterisation. The effects of this extract on cancer cells were shown to be cytotoxic rather than cytostatic. Additionally, the cytotoxic effects of EA3 were shown to be associated with controlled Ca2+ entry into the cytosol and not a rapid influx of Ca2+ indicative of necrosis. Overall, the experiments suggested that EA3-induced cytotoxicity may be due to apoptosis. The major constituents of EA3 were identified by LC-MS to be the flavonoids rutin, quercetin, luteolin, apigenin and naringenin. Several of these flavonoids are known to have cytotoxic activity in vitro and antitumour effects in vivo. However, while quercetin and luteolin alone displayed cytotoxic or cytostatic effects against the panel of cancer cell lines used in this study, they did not display bioactivity at the concentrations present in EA3. Nevertheless, due to various unknown synergistic and antagonistic interactions, it is still possible that, in combination, these known compounds were responsible for the observed cytotoxicity/cytostaticity. While there were many other compounds present in EA3 that could have explained its inhibitory effects, time constraints precluded their evaluation as the active constituent/s. Future studies will ascertain whether the observed cytotoxic effects of EA3 are due to a known or a novel compound. Chapter 7. A plant sample (Haemodorum spicatum), chosen for its purported antitumour activity, and an unexamined marine sponge, selected randomly, were screened for bioactivity. Using these examples, the ethnopharmacological approach was shown to be a relevant, but not necessarily better, strategy to selecting plants for initial screening studies. Chapter 8. This chapter is an overview of the various sections, commenting on some issues that were raised and discussing possible future directions. It was concluded that, even though a novel cytotoxic compound was not identified from this research, the bioactivity of plants used by Aboriginal communities as phytomedicines was verified. This may help these communities and perhaps even lead to marketable herbal products. Additionally, the results of these experiments may inspire future collaborative studies using traditional knowledge in the ongoing search for drugs to combat cancer and other diseases.
- Urls: http://www.nintione.com.au/resource/SavigniD_EvaluationAntiCancerPotentialTraditionalMedicines.pdf
- Publisher Location: Perth