Document Type
Thesis
Date of Award
5-2024
School/College
College of Science, Engineering, and Technology (COSET)
Degree Name
MS in Biology
Committee Chairperson
Mario Hollomon
Committee Member 1
Erica Cassimere
Committee Member 2
Hector Miranda
Committee Member 3
Jahmario Williams
Keywords
Antioxidants, FOXO, Free radicals, Oxidative stress, Reactive oxygen species, Transcription factors
Abstract
Redox homeostasis is a balance between reactive oxygen species (ROS) generation and neutralization by antioxidants. Oxidative stress (OS) results when the generation of ROS exceeds the neutralizing capacity of endogenous antioxidants. Reactive oxygen species are generated during cellular processes such as mitochondrial activity or metabolism of drugs. Expression of endogenous antioxidants is driven by redox-sensitive transcription factors; therefore, redox-sensitive transcription factors are essential for the maintenance of cellular redox homeostasis. There are several redox-sensitive transcription factors that contribute to the expression of endogenous antioxidants. These redox-sensitive transcription factors include nuclear factor erythroid 2-related factors (Nrf-2), hypoxia-inducible factor (HIF), activator protein-1 (AP-1), nuclear factor-kappa B (NF-κB) and forkhead transcription factor class O (FOXO). The objective of this research project is to determine the contribution of FOXO to redox homeostasis in osteosarcoma. Osteosarcoma is the most common bone cancer with most osteosarcoma cases occurring in people under 30 years old. In this study, FOXO1 and FOXO3 were inhibited followed by assessment of oxidative stress. Basal levels of select endogenous antioxidants were also investigated. The results of this study indicate that chemical inhibition of FOXO1 or FOXO3 increases oxidative stress in osteosarcoma. The results also indicate that different osteosarcoma cell lines express different levels of endogenous antioxidants. Collectively, the results of this study suggest that FOXO1 and FOXO3 contribute to redox homeostasis in osteosarcoma.
Copyright
Copyright © for this work is retained by the author. Any documents and information presented are protected by copyright under US Copyright laws and are the property of the author. All Rights Reserved. For permission to use this content please contact the author or the Graduate School at Texas Southern University (graduate.school@tsu.edu).
Recommended Citation
Brown, Kai K., "Inhibition Of Foxo Induces Oxidative Stress In Osteosarcoma" (2024). Theses (2016-Present). 69.
https://digitalscholarship.tsu.edu/theses/69