dc.contributor.advisor | Davis, Rohan | |
dc.contributor.author | Levrier, Claire | |
dc.date.accessioned | 2018-01-23T02:52:28Z | |
dc.date.available | 2018-01-23T02:52:28Z | |
dc.date.issued | 2016 | |
dc.identifier.doi | 10.25904/1912/3780 | |
dc.identifier.uri | http://hdl.handle.net/10072/367364 | |
dc.description.abstract | The lack of a cure for advanced prostate cancer (PCa) highlights the need for better therapies to fight this disease, which is the second most common cause of cancer-related death in men. Nature is a rich source of potent anticancer agents, as 75% of the current drugs are derived from natural products, some being microtubule-targeting drugs like vinblastine and docetaxel. While proven to increase overall survival time of PCa patients, docetaxel treatment ultimately fails in part due to the development of drug resistance, presenting a major clinical challenge, given the limited number of alternative treatments currently available.
As part of a research program aimed at identifying new anticancer compounds from nature for drug discovery and development, a pre-fractionated plant library was screened for cytotoxic activity in the PCa cell line LNCaP. This cell line is positive for the androgen receptor (AR) and is androgen-dependent; LNCaP cells are representative of advanced PCa sensitive to AR-targeted therapies. Only plants native to Australia were considered for the pre-fractionated library. A taxonomically diverse set of plants were used with 12 botanical families and 16 genera represented. The library consisted of 38 fractions obtained from C18 HPLC fractionation of 38 MeOH plant extracts, with one fraction collected for each extract. A growth inhibition assay based on metabolic activity (alamarBlue) was used to screen the 38 fractions against the PCa cell line LNCaP. Of the 38 fractions screened, six displayed inhibition of more than 50% at 10 µg/mL, which was the cut-off selected for pursuing hit fractions. Bioassay-guided fractionation and/or mass-directed isolation were performed on two plant samples, Anopterus macleayanus and Hernandia albiflora. Several cytotoxic natural products were purified and their chemical structures determined using a combination of 1D/2D NMR, MS, and UV data. | |
dc.language | English | |
dc.publisher | Griffith University | |
dc.publisher.place | Brisbane | |
dc.rights.copyright | The author owns the copyright in this thesis, unless stated otherwise. | |
dc.subject.keywords | Prostate cancer, Cure | |
dc.subject.keywords | Australian endemic plants | |
dc.subject.keywords | Docetaxel treatment | |
dc.subject.keywords | Natural therapies | |
dc.subject.keywords | Therapeutic drugs | |
dc.subject.keywords | Anopterus macleayanus | |
dc.subject.keywords | Hernandia albiflora | |
dc.title | Phytochemical and Biological Investigations of Cytotoxic Compounds from Australian Endemic Plants | |
dc.type | Griffith thesis | |
gro.faculty | Science, Environment, Engineering and Technology | |
gro.description.notepublic | Supplementary material is held on the spreadsheet and on the G:Drive. | |
gro.rights.copyright | The author owns the copyright in this thesis, unless stated otherwise. | |
gro.hasfulltext | Full Text | |
dc.contributor.otheradvisor | Sadowski, Martin | |
dc.contributor.otheradvisor | Nelson, Colleen | |
dc.rights.accessRights | Public | |
gro.identifier.gurtID | gu1493013136177 | |
gro.source.ADTshelfno | ADT0 | |
gro.source.GURTshelfno | GURT | |
gro.thesis.degreelevel | Thesis (PhD Doctorate) | |
gro.thesis.degreeprogram | Doctor of Philosophy (PhD) | |
gro.department | School of Natural Sciences | |
gro.griffith.author | Levrier, Claire | |