Development of a Novel Anticancer Therapy by Targeting Apoptotic Signalling Pathways

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Wei, Ming
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Mellick, Albert
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This PhD project aimed to examine the anticancer potential of a natural compound, cinobufagin (CBF), and the signal transduction pathways involved in CBF-induced cell death, especially pro-apoptotic pathways. CBF is a major component of the traditional Chinese medicine Chansu, which is extracted from parotoid glands of Chinese toads. Chansu has been widely used in the treatment for inflammation in China for centuries. The role of Chansu in anti-neoplasm has recently been revealed and it leads to a new area of research. In this study, CBF was initially found to have a potent capacity for anti-proliferation in a variety of cancer cell lines. Our result from cytotoxicity assays showed a particular high sensitivity of CBF in human colon cancer cell lines. Thus, HCT116 and HT29 cell lines were selected for the further investigations. To clarify whether the cell death induced by CBF is apoptosis or necrosis, Annexin V staining was carried out and showed a consequence of CBF-induced apoptosis in both cell lines. The subsequent detection of mitochondrial potential changes post CBF exposure was discovered in the two cell lines. However, the apoptotic pathways elicited by CBF were different in HCT116 and HT29 cells. CBF activated Caspase-3 in HCT116 cells, but the activity of Caspase-3 in treated HT29 cells was inhibited. The translocation of mitochondrial apoptosis inducing factor (AIF), a crucial protein for Caspase-3-independent apoptosis, was also detected but only in HCT116 cells. The nuclear import of AIF was untraceable in the process of HT29 cell death during CBF treatment. Altogether, we concluded that CBF-induced apoptosis in HCT116 is through both Caspase-3 dependent and independent pathways, while the apoptotic signalling pathways in treated HT29 cells are still undiscovered.

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Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School of Medical Science
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Cinobufagin (CBF)
CBF-induced cell death
Chinese medicine Chansu
Colon cancer
Novel anticancer therapy
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