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dc.contributor.advisorGiles, Greg
dc.contributor.authorDeuss, Felix
dc.date.available2012-10-30T19:48:02Z
dc.date.copyright2012
dc.identifier.citationDeuss, F. (2012). The Oxidative Modifications to Cancer Cells Induced by Three Redox-Active Drugs: Auranofin, PEITC and TDSNO (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/2525en
dc.identifier.urihttp://hdl.handle.net/10523/2525
dc.description.abstractRedox homeostasis is of critical importance for normal cellular functions. The intracellular environment is maintained in a reduced state, upon which, reactive oxygen (ROS) and nitrogen (RNS) species oxidise cellular components and induce functional changes. Proteins are important targets of redox signalling, as their diverse cellular functions may be regulated by the oxidation of specific amino acid residues. The thiol groups of cysteine residues are particularly important due to their roles in activity, intra- and inter-molecular bonding. Abnormalities in the cellular redox state underlie many forms of cancer; these exhibit a shift in the redox balance towards a more oxidative state. Therefore, the pharmacological induction of oxidative modifications to the proteome will selectively induce death in cancer cells. This study aimed to assess the chemical changes induced by three redox-active drugs, auranofin, PEITC and a novel light-sensitive S-nitrosothiol, known as TDSNO, because of their potential thiol modifying activity. A therapeutic range was established for each drug and FTIR spectroscopy was used to identify the chemical effects induced by non-toxic and cytotoxic concentrations. All three compounds induced significant changes to the proteome, however TDSNO and PEITC induced additional minor changes to other cellular components. Non-toxic concentrations of both auranofin and PEITC induced larger chemical changes than cytotoxic concentrations, while a linear correlation to the photo-activated TDSNO concentration was observed. Despite the differences, the changes induced by the three drugs were predominantly co-localised with the nucleus and potentially the endoplasmic reticulum. Furthermore, it was found that the modulation of the glycolytic pathway altered the cytotoxicity of TDSNO. There is therefore potential for these drugs to be used in combination and in the presence of inhibitors of glycolysis, for the selective treatment of cancer.
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectFTIR
dc.subjectInfrared
dc.subjectSpectroscopy
dc.subjectSynchrotron
dc.subjectAuranofin
dc.subjectPEITC
dc.subjectPhenethyl Isothiocyanate
dc.subjectTDSNO
dc.subjectRedox
dc.subjectPharmacology
dc.subjectCancer
dc.titleThe Oxidative Modifications to Cancer Cells Induced by Three Redox-Active Drugs: Auranofin, PEITC and TDSNO
dc.typeThesis
dc.date.updated2012-10-30T10:03:20Z
dc.language.rfc3066en
thesis.degree.disciplinePharmacology & Toxicology
thesis.degree.nameMaster of Science
thesis.degree.grantorUniversity of Otago
thesis.degree.levelMasters
otago.interloanno
otago.openaccessAbstract Only
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