An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer

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dc.contributor.advisorHendricks, Denveren_ZA
dc.contributor.authorShunmoogam-Gounden, Nelushaen_ZA
dc.date.accessioned2015-07-01T08:59:57Z
dc.date.available2015-07-01T08:59:57Z
dc.date.issued2014en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractCurrent 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.en_ZA
dc.identifier.apacitationShunmoogam-Gounden, N. (2014). <i>An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry. Retrieved from http://hdl.handle.net/11427/13237en_ZA
dc.identifier.chicagocitationShunmoogam-Gounden, Nelusha. <i>"An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2014. http://hdl.handle.net/11427/13237en_ZA
dc.identifier.citationShunmoogam-Gounden, N. 2014. An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Shunmoogam-Gounden, Nelusha AB - 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. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer TI - An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer UR - http://hdl.handle.net/11427/13237 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13237
dc.identifier.vancouvercitationShunmoogam-Gounden N. An investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal cancer. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Medical Biochemistry, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/13237en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedical Biochemistryen_ZA
dc.titleAn investigation into the molecular mechanisms induced by derivatives of natural products in oesophageal canceren_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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