A major challenge in cancer therapy is the emergence of acquired resistance to a wide range of chemotherapeutic drugs with unrelated structures and activities. Possible mechanisms to explain drug resistance are induction of efflux pumps, activation of scavenging pathways and/or changes in the oncogene status of a cell. A number of studies have shown that overexpression of Bcl-2 confers resistance by preventing drug induced apoptosis. In this thesis, Madin Darby canine kidney epithelial (MOCK) cells were used to investigate the relationship between cisplatin resistance and Bcl-2 expression. In our studies overexpression of Bcl-2 was sufficient in preventing apoptosis induced by serum deprivation. However, treatment with varying cisplatin doses did not induce an apoptotic response. Electron microscopy and in situ DNA end labelling experiments show changes distinct from those associated with serum deprivationinduced apoptosis. Survival as assessed by DNA fluorometry and clonogenic assays clearly demonstrate that the overexpression of Bcl-2 fails to protect against the cytotoxic effects of cisplatin in MOCK cells. Our results show that cisplatin induces a form of cell death distinct from apoptosis and suggests that multiple pathways to cell death exist which are differentially regulated in a cell type-specific and stimuli-specific fashion. / Thesis / Master of Science (MS)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23365 |
| Date | 04 1900 |
| Creators | Srivastava, Anupma |
| Contributors | Singh, Gurmit, Biochemistry |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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