Graduation Year
2024
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 Jiang, Ph.D.
Committee Member
Francis Ntumngia, Ph.D.
Committee Member
Bi Zhao, Ph.D.
Keywords
ALA, Cancer biology, Cancer therapeutics, DHA, Drug repurposing, Heme metabolism
Abstract
The increased understanding of cancer cell metabolism has shown options for novel treatment strategies. This thesis looks at the role of heme metabolism, specifically "porphyrin overdrive," in cancer progression and treatment. Cancer cells are hypermetabolic and rely on heme synthesis. When treated with δ-aminolevulinic acid (ALA), they abnormally accumulate heme intermediates. This metabolic weakness presents an opportunity to exploit heme synthesis in targeted cancer therapy. In this study, we suggest a "Bait and Kill" technique that uses exogenous ALA to induce protoporphyrin IX (PpIX) buildup in cancer cells, making them more susceptible to oxidative stress. We investigate the possibility of combining ALA and dihydroartemisinin (DHA), an artemisinin derivative, to increase this vulnerability. This combination medication exhibits strong anticancer effects at lower concentrations than DHA alone, suggesting a potentially less hazardous alternative to standard therapies.Furthermore, the study investigates the use of antimicrobial peptides (AMPs), specifically NCR247, which has a high heme affinity. NCR247 has heme sequestration properties, which reduce heme availability and cause cancer cell death. The study also looks at the synergistic effects of NCR247 with ALA and hemin, indicating its potential as a therapeutic drug. The findings are validated in various cancer cell types, including liver and glioblastoma cell lines, suggesting the broad applicability of these treatment approaches. The data from this study expands our understanding of cancer-specific metabolic pathways and presents novel methods for cancer treatment, highlighting the need for additional molecular research, including preclinical and clinical trials to optimize therapeutic regimens.
Scholar Commons Citation
Meshram, Pravin D., "Porphyrin Overdrive in Cancer: Unraveling the Mechanisms and Therapeutic Potential" (2024). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10538
