DOI
https://doi.org/10.25772/CH28-SJ05
Defense Date
2020
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Janina P. Lewis
Abstract
Iron plays a critical role in life sustaining functions for the cell. Dysregulation of these processes can be an issue with maintaining homeostatic conditions. Various cancer types have been observed to show malfunction in the maintenance of their iron homeostasis, in particular with the iron export protein—ferroportin. Ferroportin is the sole iron exporter known. Its structure and mechanism have not fully been elucidated yet, but its modulation has been associated with a poorer prognosis in cancers like breast, leukemia, prostrate, ovarian, colorectal, etc. Decreased iron exportation by ferroportin may lead to an increased labile iron pool allowing the cell to be more susceptible to the generation of reactive oxygen species. Reactive oxygen species in turn interact with cell membrane lipids producing lipid peroxides and create membrane integrity issues. This results in a form of cell death known as ferroptosis. We show that ferroportin is present in oral cancer cells and its expression is altered between different oral cancer cell types. We tested the efficacy of indirect ferroptosis inducers, erastin and Sulfasalazine, as well as employed an experimental iron overloading drug Feraheme. We observed a level of sensitivity with the low ferroportin expressing cells.
Rights
©Ashley N. Hemingway
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-30-2020