Title

The Potential Effects of NGR-Tagged, Ruthenium-Substituted Rubredoxin on APN/CD13- Expressing Cancer Cells

Date of Award

7-2020

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Francis E Jenney, Jr, PhD

Second Advisor

Kimberly Baker, PhD

Third Advisor

Eric Wang, PhD

Fourth Advisor

Richard White, PhD

Abstract

Cancer is the second leading cause of death in the world, accounting for an estimated 9.6 million fatalities in a study conducted by the World Health Organization in 2018. Traditional treatments for cancer include chemotherapy, surgical excision, and monoclonal antibodies. Cisplatin, a novel platinum-based chemotherapeutic, has been the frontline for cancer therapy in conjunction with secondary cancer treatments such as monoclonal antibody therapy. As effective as these treatments are, there are drawbacks to each form. The lack of specificity and increased cytotoxic side effects from chemotherapeutics has encouraged cancer research to pursue different avenues for treatment. Ruthenium is a known cytotoxic metal within the family of platinum that has shown significant results in cell cytotoxicity by binding to DNA and inducing apoptosis. Rubredoxin, a protein from the hyperthermophile Pyrococcus furiosus, is an extremely stable protein that may act as an ideal vehicle to introduce ruthenium to cancerous cells. By mutating rubredoxin to contain an NGR-homing peptide, we expect rutheniumsubstituted NGR-tagged rubredoxin will bind to cancer cells expressing APN/CD13 receptors and induce apoptosis.

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