|dc.description.abstract||Objective: To evaluate the anti-cancer effects of C20E in human cell lines representative of cervical (HeLa), liver (HEPG2), lung (A549), prostate (DU145), placental (BeWo) and breast (MDA-MB-468) tumours.
Methods and Results: After treatment with C20E, cell proliferation was estimated by mitochondrial MTT reduction, cell viability by ATP production and apoptosis by caspase 3/7 activity. C20E decreased MTT reduction in all cell lines in a concentration-dependent fashion (by 30±4%-76±15% from control at 40 µM, 48 hours of treatment). C20E significantly impaired ATP production to 51±8.4%, 6.1±1.2%, 77.1±5.1%, 70.3±7.9% relative to control (40 µM, 48 hours) in A549 lung carcinoma, BeWo placental choriocarcinoma, DU145 prostate carcinoma and HeLa cervical adenocarcinoma cells, respectively. C20E did not significantly impair ATP production in HEPG2 hepatocellular adenocarcinoma and MDA-MB-468 breast adenocarcinoma cells. Similarly, caspase 3/7 activity was increased by 26±4%-49±8% over control. To pursue these findings, cell cycle kinetics were analysed in propidium iodide-stained cells. Treatment with C20E (40 µM, 48 hours) increased the proportion of cells in the G0 and G1 phase whilst decreasing the proportion of cells in the S phase and G2/M phase, except for BeWo placental choriocarcinoma cells. Western immunoblotting for cyclin D1 was undertaken because this protein regulates the G1 to S phase transition, and was down regulated in MDA-MB-231 breast adenocarcinoma cells by C20E. A decrease in cyclin D1 expression at 40 µM in A549, DU145, HeLa, HEPG2 and MDA-MB-468 cancer cell lines occurred after 48 hours of C20E treatment but not in BeWo cells.
Conclusion: C20E decreased the viability of multiple cancer cell lines by inhibiting cell cycle progression, likely due to cyclin D1 down-regulation and also increased apoptosis. The responsiveness of A549, DU145 and HeLa cell lines suggests that further testing in lung, prostate and cervical cancer models is warranted.||en_AU|
|dc.publisher||University of Sydney||en_AU|
|dc.publisher||Sydney Medical School||en_AU|
|dc.publisher||Discipline of Pharmacology||en_AU|
|dc.rights||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.||en_AU|
|dc.title||The Antiproliferative and Pro-Apoptotic Effects of a Synthetic Omega-3 Epoxyfatty Acid Analogue in Different Human Cancer Cell Lines||en_AU|
|dc.type.pubtype||Master of Philosophy M.Phil||en_AU|
|dc.description.disclaimer||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.||en_AU|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|