Growth Inhibition by Selenium Compounds

Blower, Lorraine (1998) Growth Inhibition by Selenium Compounds. MSc(R) thesis, University of Glasgow.

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Abstract

A number of selenium compounds have been shown to have anticancer properties. The mechanism by which selenium has anticarcinogenic effects is not understood although it is likely to be related to its ability to inhibit cell growth and induce apoptosis. The mechanism by which selenium compounds induce apoptosis is also not understood although it has been hypothesised that selenite induces cell death during Its reduction to hydrogen selenide by the generation of reactive oxidant species resulting in oxidative stress. Bcl-2 has been shown to inhibit the ability of a number of stimuli to cause apoptosis possibly by its ability to prevent the effects of reactive oxygen species and peroxides. The aim of this project was therefore to investigate whether Bcl-2 could inhibit cell death induced by two selenium compounds; selenodiglutathione (SDG), the primary metabolite of selenite and 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a novel synthetic selenium compound. The first part of the thesis work describes the preparation of SDG and optimisation of conditions for growth inhibition by SDG and p-XSC. The second part of the thesis describes studies to test whether over-expression of Bcl-2 could protect cells from cell death induced by selenium compounds. MCF7 cells, a human breast cell line, were transfected with a Bcl-2 expression vector by electroporation and selected for resistance to G418, the selection marker. By western blotting of cell lysate and detection with anti-Bcl-2 antibodies, a number of clones were demonstrated to over-express Bcl-2 protein. By the use of cell proliferation and cloning assays it was demonstrated that clones over-expressing Bcl-2 protein were equally sensitive to cell death induced by selenium compounds SDG and p-XSC as cells transfected with vector control. As Bcl-2 over-expression in a haemopoetic cell line has previously been shown to protect against apoptosis induced by H2O2, it was also tested if the clones produced in this study to over-express Bcl-2 were able to prevent H2O2 induced cell death. From the results of the cell proliferation and cloning assays, cells with over-expression of bcl-2 did not appear to be more resistant to H2O2 induced cell death than control cells. Thus, in this study Bcl-2 overexpression was found not to provide protection against SDG, p-XSC or H2O2 induced cell death in MCF7 cells.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: Paul Harrison
Keywords: Medicine
Date of Award: 1998
Depositing User: Enlighten Team
Unique ID: glathesis:1998-75923
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Dec 2019 09:15
Last Modified: 19 Dec 2019 09:15
URI: http://theses.gla.ac.uk/id/eprint/75923

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