Honors Theses
Targeting G-Quadruplexes within the ADAM-15 Promoter: A Novel Therapeutic Approach for Breast Cancer
Date of Award
2015
Document Type
Undergraduate Thesis
Department
Biomolecular Sciences
First Advisor
Tracy Brooks
Relational Format
Dissertation/Thesis
Abstract
ADAM-15 is a protein that is up-regulated in many diseases, particularly breast cancer; its over-expression is correlated with more aggressive and invasive phenotypes. The critical core promoter region of ADAM-15 is capable of forming a secondary DNA structure known as a G-quadruplex. The stabilization of this G-quadruplex has the potential to decrease the transcription of the over-expressed ADAM-15 protein. Six hundred forty compounds were screened for their ability to cause a shift in the melting temperature of an ADAM-15 oligonucleotide using FRET melt. Two compounds, NSC 146771 and NSC 260594, produced a significant shift in the melting temperature; further experimentation, such as circular dichroism, cytotoxicity MTS assays, and RT-qPCR, was performed to confirm the ability of these small molecules to stabilize the G-quadruplexes within the ADAM-15 promoter. Neither compound showed cytotoxicity, and NSC 260594 showed an increased capacity for reducing the transcription of ADAM-15. Further pharmacokinetic and pharmacodynamic experimentation needs to be completed, but NSC 260594 shows potential to significantly decrease ADAM-15 expression and therefore improve the prognosis of breast cancer patients.
Recommended Citation
Jenkins, Rachel L., "Targeting G-Quadruplexes within the ADAM-15 Promoter: A Novel Therapeutic Approach for Breast Cancer" (2015). Honors Theses. 772.
https://egrove.olemiss.edu/hon_thesis/772
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