Graduation Date

Fall 12-16-2022

Document Type

Dissertation

Degree Name

Master of Science (MS)

Programs

Biochemistry & Molecular Biology

First Advisor

Ming-Fong Lin, Ph.D.

Second Advisor

Melissa Teoh, Ph.D.

Third Advisor

Rebecca E. Oberley-Deegan, Ph.D.

Fourth Advisor

Armen Petrosyan, Ph.D.

Abstract

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in the U.S. in men, mainly due to the development of castration-resistant PCa (CRPC). MnTnBuOE-2-PyP5+ (BuOE), a superoxide dismutase (SOD) mimic, inhibits human PCa cell proliferation through hydrogen peroxide (H2O2). p66Shc protein level is upregulated in CRPC and is associated with cell proliferation in PCa cells.We propose that the different sensitivity of those PCa cells to BuOE could be due to the expression levels of p66Shc protein.

Our data showed that PCa cells that expressed high levels of p66Shc are more resistant to BuOE treatments compared to cells that expressed low level of p66Shc. Even though BuOE has an inhibitory effect on p66Shc and nuclear factor erythroid 2- related factor 2 (Nrf2) protein expressions in our PCa cells, reductions of p66Shc and Nrf2 in cells that express a high level of p66Shc are not correlated with a reduction in cell proliferation. It is suggested that the mechanism by which cells with a high level of p66Shc are resistant to BuOE treatments does not depend on Nrf2/p66Shc pathway. It was unclear the exact mechanism that cells expressing a high level of p66Shc are more resistant to BuOE. It is important to look further into other factors that could contribute to BuOE resistance.

Comments

2022 Copyright, the authors

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