Novel roles for manganese superoxide dismutase polymorphisms in prostate cancer, 2021
Sweeney, Janae D.
2021-05
2020-2029
Epithelial Mesenchymal Transition (EMT), a key event in cancer metastasis, allows polarized epithelial cells to assume mesenchymal morphologies, enhancing invasiveness and migration, and can be induced by Reactive Oxygen Species (ROS). Val16A (Ala) Superoxide Dismutase (SOD2) polymorphism has been associated with increased prostate cancer (PCa) risk. We hypothesized that SOD2 Ala single nucleotide polymorphism (SNP) may promote EMT. SOD2 expression and genotype was analyzed in various prostate cell lines. Stable overexpression of Ala-SOD2 or Val-SOD2 allele was performed in LNCaP cells followed by analysis of intracellular ROS and EMT marker protein expression. Treatments were performed with muscadine grape skin extract (MSKE) antioxidant, with or without addition of H2O2 to provide further oxidative stress. Furthermore, MTS cell proliferation, cell migration, and apoptosis assays were completed. The results showed that SOD2 expression did not correlate with tumor aggressiveness nor SOD2 genotype. Ala-SOD2 allele was demonstrated to be associated with marked induction of EMT indicated by higher Snail and vimentin, lower E-Cadherin, and increased cell migration, when compared to Val-SOD2 allele or Neo control cells. Ala-SOD2 SNP cells exhibited increased levels of total ROS and superoxide and were more sensitive to co-treatment with H2O2 and MSKE, which led to reduced cell growth and increased apoptosis. Additionally, MSKE inhibited Ala-SOD2 SNP-mediated EMT. The data indicates that treatment with a combination of H2O2-generative drugs, such as certain chemotherapeutics, and antioxidants such as MSKE that targets superoxide, hold promising therapeutic potential to halt PCa progression in the future.
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Atlanta University and Clark Atlanta University Theses and Dissertations
dissertation
Doctor of Philosophy (PhD)
Clark Atlanta University
Department of Biological Sciences
Odero-Marah, Valerie
Georgia--Atlanta
http://hdl.handle.net/20.500.12322/cau.td:2021_sweeney_janae_d
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