Date of Award
Chemistry and Biochemistry
Pure sciences, Biological sciences
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Cancer is a devastating disease, affecting millions of individuals every year. Though no cure exists for cancer at present, countless years of research have given rise to promising treatments such as Trastuzumab, Taxol, Tamoxifen, VP-16 and cisplatin. The majority of these treatments are non-selective thus affecting both normal and cancerous cells. Pancratistatin, a natural compound obtained from the Hawaiian spider lily, is known to be specific and selective in inducing apoptosis in multiple cancer cell lines through selectively targeting the mitochondria. In this study it was discovered that PST induced increased levels of cytosolic pro-apoptotic protein Bad in the cytoplasm as well as localization of Bax to the mitochondrial membrane. Release of Cytochrome c due to membrane permeabilization indicating the activation of the mitochondrial (intrinsic) pathway of apoptosis was initiated.
Tamoxifen is a known anti-estrogen compound, which has the capability to induce apoptosis in estrogen receptor dependent breast cancers selectively. This compound is relatively non-toxic to normal cells. Recently, it was reported that Tamoxifen has the capability of destabilizing mitochondrial membrane potential. In combination with the anti-estrogen Tamoxifen, PST had a synergic effect in both estrogen receptor positive as well as estrogen receptor negative cells at lower doses than previously reported. Furthermore, whole cell reactive oxygen species levels were increased and mitochondrial destabilization was observed. Thus the present work provides evidence to support the observation that Tamoxifen might work through mechanisms distinct from the canonical estrogen receptor antagonism and act synergistically with PST.
Siedlakowsk, Peter, "Synergistic effect of PST and Tamoxifen in inducing apoptosis by targeting the mitochondria and insights into novelty of PST induced apoptosis" (2008). Electronic Theses and Dissertations. 8026.