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An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer
Includes bibliographical references.
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Division of Medical Biochemistry
2015
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| _version_ | 1867614302021615616 |
|---|---|
| access_status_str | Open Access |
| author | Shunmoogam-Gounden, Nelusha |
| author2 | Hendricks, Denver |
| author_browse | Hendricks, Denver Shunmoogam-Gounden, Nelusha |
| author_facet | Hendricks, Denver Shunmoogam-Gounden, Nelusha |
| author_sort | Shunmoogam-Gounden, Nelusha |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/13237 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:49:52.791Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Division of Medical Biochemistry |
| publisherStr | Division of Medical Biochemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/13237 An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer Shunmoogam-Gounden, Nelusha Hendricks, Denver Medical Biochemistry Includes bibliographical references. Current chemotherapies for oesophageal cancer display poor efficacy and tolerability, highlighting an unmet need for novel chemotherapeutic agents. Artemisinin derivatives, currently used to treat malaria, were recently shown to possess potent anticancer activity. This study investigated the potential of two first generation artemisinin derivatives (artesunate and dihydroartemisinin), together with novel artemisinin hybrid compounds, as cancer chemotherapeutic agents and explored the mechanism of action in oesophageal cancer. Artesunate and dihydroartemisinin including seventeen other artemisinin derivatives were screened against oesophageal cancer cells using the 3 - [4,5-dimethylthiazol-2 -yl]-2,5 - diphenyltetrazolium bromide (MTT) assay and GraphPad Prism Software to calculate IC 50 (50% inhibitory concentration) values. Novel halogenated artemisinin - isatin hybrid compounds displayed the best activity against oesophageal cancer cells, and were more potent than artesunate and dihydroartemisinin in a small panel of oesophageal, breast and cervical cancer cell lines tested. The novel derivatives induced a G0/ G1 cell cycle arrest whilst the parental compounds induced a G2/ M block of the cell cycle, using flow cytometry. This suggested a different mechanism of action for the novel compounds. Dihydroartemisinin and the most active novel hybrid, EXP57EA, were investigated to understand their molecular mechanisms of action in oesophageal cancer. 2015-07-01T08:59:57Z 2015-07-01T08:59:57Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/13237 eng application/pdf Division of Medical Biochemistry Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medical Biochemistry Shunmoogam-Gounden, Nelusha An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| thesis_degree_str | Doctoral |
| title | An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| title_full | An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| title_fullStr | An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| title_full_unstemmed | An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| title_short | An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| title_sort | investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer |
| topic | Medical Biochemistry |
| url | http://hdl.handle.net/11427/13237 |
| work_keys_str_mv | AT shunmoogamgoundennelusha aninvestigationintothemolecularmechanismsinducedbyderivativesofnaturalproductsinoesophagealcancer AT shunmoogamgoundennelusha investigationintothemolecularmechanismsinducedbyderivativesofnaturalproductsinoesophagealcancer |