Raphael, Brooke (2021) The cytotoxic properties of novel compounds from a Preussia sp. isolate on PC-3 prostate cancer cells. Honours thesis, University of Southern Queensland. (Unpublished)
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Text (Thesis (Honours))
Brooke Raphael BSc (Hons) Final Thesis.pdf Available under License Creative Commons Attribution Non-commercial No Derivatives 4.0. Download (4MB) | Preview |
Abstract
Prostate cancer (PCa) is the most commonly diagnosed cancer amongst Australian males. The significant economic and healthcare burden caused by PCa requires immediate action. Although chemotherapies such as docetaxel can be successful as a first line treatment for metastatic castration-resistant PCa (mCRPC), chemo-resistance and disease progression can develop. Therefore, novel drugs are in need of discovery.
Endophytic microfungi have potential as new sources of anticancer chemotherapy agents as they can be sustainably acquired and are capable of large-scale and low-cost production. Many antifungal and antibacterial compounds sourced from endophytes have also been demonstrated to cause cytotoxicity in cancer cell lines. These chemotherapy agents act as mitotic inhibitors, signal transduction disruptors, and topoisomerase inhibitors. The present study investigates the cytotoxic properties that a previously studied endophytic Preussia sp. may possess, given that polyketides extracted from this isolate were reported to be antibacterial and antifungal in nature. Cytotoxic polyketides from other Preussia spp. have been reported to disrupt the cytoskeleton of prostate cancer cell lines and cause apoptosis. Therefore, evidence of cytoskeletal disruption and apoptosis were the tested mechanisms of action in this study.
The antimicrobial activity of the Preussia sp. isolate was initially confirmed by co-culturing with pathogenic bacteria and fungi on solid media. The isolate was next grown in a bulk culture, and ethyl acetate (EtOAc) extracts were obtained and re-tested against Bacillus cereus and Enterococcus faecalis. EtOAc extracts were then separated into fractions via high performance liquid chromatography (HPLC). These fractions were tested using an in vitro model of castration resistant PCa (CRPC), the PC-3 cell line, at varying concentrations in order to investigate any cytotoxic effects. Treated cells were also visualised with fluorescence microscopy to investigate changes to cytoskeletal and nuclear structures.
The cell counting kit (CCK-8) assay revealed that several fractions had a negative effect on cell proliferation and so were potentially cytotoxic at pharmaceutically relevant concentrations. Fraction four at 50 µg/mL decreased live cell number by 16% (p=0.0355). Fraction five at 50 µg/mL and 100 µg/mL reduced live cell number by 25% (p=0.0415) and 28.5% (p=0.0082), respectively. Fraction six at 50 µg/mL and 100 µg/mL decreased live cell number by 32.4% (p=0.0009) and 87.4% (p<0.0001), respectively. Cytoskeletal and nuclear structure studies using microscopy did not reveal any consistent changes amongst the replicate treated cells suggesting that the decrease in cell number that was observed may have been caused by non-apoptotic mechanisms. Therefore, this study provides significant evidence that this endophytic isolate may contain important anti-cancer compounds.
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| Item Type: | Thesis (Non-Research) (Honours) |
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| Item Status: | Live Archive |
| Faculty/School / Institute/Centre: | Historic - Faculty of Health, Engineering and Sciences - School of Sciences (6 Sep 2019 - 31 Dec 2021) |
| Supervisors: | Dearnaley, John; Whiteside, Eliza; Lynch, Mark |
| Qualification: | Bachelor of Science (Honours) |
| Date Deposited: | 20 Dec 2021 23:23 |
| Last Modified: | 28 Feb 2024 01:47 |
| Uncontrolled Keywords: | Endophyte, cytotoxic, prostate cancer, anti-cancer, PC-3, antimicrobial, microtubule. |
| Fields of Research (2008): | 11 Medical and Health Sciences > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology 06 Biological Sciences > 0605 Microbiology > 060505 Mycology |
| Fields of Research (2020): | 31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310705 Mycology 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321101 Cancer cell biology |
| Socio-Economic Objectives (2008): | C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders |
| URI: | https://sear.unisq.edu.au/id/eprint/46084 |
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