Targeting G-Quadruplexes within the ADAM-15 Promoter: A Novel Therapeutic Approach for Breast Cancer

Jenkins, Rachel L. (2015) Targeting G-Quadruplexes within the ADAM-15 Promoter: A Novel Therapeutic Approach for Breast Cancer. Undergraduate thesis, under the direction of Tracy A. Brooks from Department of BioMolecular Sciences, The University of Mississippi.

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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.

Item Type: Thesis (Undergraduate)
Creators: Jenkins, Rachel L.
Student's Degree Program(s): B.S. in Pharmaceutical Sciences
Thesis Advisor: Tracy A. Brooks
Thesis Advisor's Department: Department of BioMolecular Sciences
Institution: The University of Mississippi
Subjects: R Medicine > RM Therapeutics. Pharmacology
Depositing User: Rachel Jenkins
Date Deposited: 07 May 2015 16:05
Last Modified: 07 May 2015 16:05
URI: http://thesis.honors.olemiss.edu/id/eprint/370

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