Thesis (Ph. D.), Faculty of Health Sciences, University of the Witwatersrand, 2009 / With the high prevalence and high mortality rate of cancer in the global community, it is
increasingly essential to accelerate our understanding of the disease, to identify new
genetic targets for therapy, and to pursue avenues for improving on the therapies in
development and in current use. The aim of this study is to identify cell cycle-related
genes whose expression is influenced by the chemotherapeutic drugs curcumin, SAHA,
lycopene and thalidomide in breast and colon cancer and normal cell lines. These drugs
are currently not in clinical use for cancer in South Africa, and while there have been
investigative studies of these chemotherapeutic agents, this study aims to identify the
specific genes that are influenced by the drugs. The result of this is that several genes
that were not previously documented as targets of these drugs are highlighted. The cell
cycle pathway is the area of focus as loss of regulation in the cell cycle is one of the
important factors involved in promoting cancer initiation and progression.
In the first instance, flow cytometry was used to identify optimal drug concentrations
relative to the cell cycle stages. Following this, alterations in gene expression were
assessed using a PCR-based differential display after each drug treatment. Subsequently,
a more focussed approach was taken in a PCR-array analysis of panels of cell cyclerelated
genes.
A subset of genes is identified that is implicated in oncogenic transformation in breast
cancer. This has the potential to inhibit the genetic pathways involved in breast
malignancy by providing targets that perhaps may not be manipulated in current
therapies. The gene expression studies here suggest that lycopene and thalidomide
function in inhibiting this transformation, and play significant roles in suppressing the
oncogenic state of breast cancer. Curcumin and SAHA also exhibit important functions
in inhibiting tumourigenesis in colon cancer. While the results propose that the drugs
have clear roles in inhibiting breast and colon cancer, they are also implicated in
promoting cancer. This research has defined the genes that must be carefully monitored
during drug administering as they may promote these and other cancers. The availability
of these results to researchers will aid in selecting the criteria for assessing the success
rate of these drugs.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7479 |
| Date | 27 January 2010 |
| Creators | Rupnarain, Charleen |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf, application/pdf, application/pdf |
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