M.Sc. / Statistics provided by the World Health Organization state that cancer accounted for 7.9 million deaths worldwide in 2007, with numbers expected to increase to over 12 million by the year 2030. The transformation of a normal cell to a malignant tumour is known to be the result of a set of several key mutations in the genome of a normal cell, resulting in several unique properties including the evasion of programmed cell death, or apoptosis. Exacerbation of this cell death evasion can occur by overexpression of cell survival effectors such as heat shock proteins (Hsps), which are a family of highly conserved proteins that are rapidly induced in response to a variety of stresses in order to protect the cell from death. These proteins perform this function both by assisting in protein folding and therefore acting as molecular chaperones and also by directly interacting with the apoptotic machinery to prevent the initiation of cellular death. Various Hsps interfere at a range of sites in the intrinsic apoptotic pathway, both upstream of the mitochondria, and downstream at the sites of caspase activation. Similarly, Hsps also interfere at various sites in the extrinsic pathway, the caspase-independent pathways, and also function to promote the activity of survival pathways. Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known for their anti-inflammatory properties via inhibition of cyclooxygenase (COX) enzymes. These drugs have also been shown to induce apoptosis in a variety of cancer cell lines as well as decrease the risk of the development of various cancers. Interestingly, NSAIDs have additionally been shown to have the curious property of activating the heat shock transcription factor (HSF1) at concentrations much higher than that required for inhibition of COX activity. The combination of NSAIDs and hyperthermia has resulted in seemingly contradictory evidence, where some studies show that this combination leads to thermotolerance and resistance to further treatments, whilst other studies have shown that this combination directly leads to cell death or indirectly sensitizes cells to subsequent stress.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:2848 |
| Date | 20 August 2012 |
| Creators | Orsmond, Colette |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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