Graduation Year
2021
Document Type
Thesis
Degree
M.S.P.H.
Degree Name
MS in Public Health (M.S.P.H.)
Degree Granting Department
Public Health
Major Professor
Rays H. Jiang, Ph.D.
Keywords
ALA, Ferroptosis, Heme-Overdrive, RSL3
Abstract
Cancer cells are characterized by their ability to grow and proliferate in rates that far exceed normal cells by modifying their iron/heme metabolisms to levels higher than normal. This imbalance of heme biosynthesis can lead to cancer cells having a flux of heme intermediates to the point where they enter a state called heme-overdrive. Heme-overdrive is a process unique to a variety of cancers but absent in normal tissues. With this enhanced production, heme can act as an epigenic regulator for signaling proliferation (18). Through the novel strategy called ‘bait-and-kill,’ cancer cells will be coerced into a state of heme overdrive then killed through an iron-dependent, non-apoptotic, regulatory cell death called ferroptosis. However, cancer cells can vary from each other meaning that their sensitivity to the same ferroptosis inducer may differ.
The cell lines that were utilized in this research were two erythroleukemic cell lines K562 and HEL. Both specimens are iron-dependent but have different metabolic networks which results in as differential sensitivity to ferroptosis. In summation, our research discovered that heme-overdrive is a common biological strategy expressed exclusively in cancers that enhances rapid production of heme for rapid proliferation and growth but is vulnerable to ferroptosis; and utilizing our ‘bait-and-kill’ strategy we can target this unique, and exploitable, vulnerability to destroy it.
Scholar Commons Citation
Marinescu, Christopher G., "Bait-and-Kill: Targeting a Novel Heme Biochemical Pathway in Hundreds of Cancers" (2021). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/8825
