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

Available for download on Tuesday, April 29, 2025

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