The Potential of Ruthenium-substituted, NGR-tagged Rubredoxin to Act as a Cancer Therapeutic Drug
Date of Award
Master of Science in Biomedical Sciences
Francis E Jenney, Jr, PhD
Kimberly Baker, PhD
Abigail Hielscher, PhD
Richard White, PhD
Most cancer treatments have unwanted side effects due to the lack of selectivity of the treatment. Pyrococcus furiosus is a hyperthermophile that grows optimally at extreme temperatures. A protein of particular interest produced by P. furiosus is called rubredoxin (PfRd). PfRd is a highly stable, non-heme, iron-containing protein. The iron core is held in place by four cysteinyl sulfur ligands. PfRd has unique properties that make the protein a potentially valuable medical tool, including stability under extreme conditions. Previous work has shown ruthenium-substituted, NGR-tagged rubredoxin (RuRd-NGR) binds to the Aminopeptidase-N/CD13 (APN/CD13) receptor on human fibrosarcoma (HT- 1080) cells. Once bound, apoptosis is induced, ultimately killing the cells. The purpose of the project is to examine RuRd-NGR as a potential selective cancer therapeutic drug. E. coli cells were transformed with a plasmid that allowed for the expression of NGR-tagged rubredoxin. Following expression, NGR-tagged rubredoxin was purified and the native iron atom was substituted with a ruthenium atom, a known cytotoxic metal. The NGR tumor-homing peptide conferred binding specificity to the APN/CD13 receptor on HT-1080 cells, as shown via a binding assay and binding competition assay. Additionally, the RuRd-NGR treatment group caused significant cell death in the HT-1080 cell line (p<0.001 ), but not in the control, MCF-1 Oa, cell line. These results suggest that RuRd-NGR has potential to act as a targeted cancer therapeutic drug.
Farah, Alina, "The Potential of Ruthenium-substituted, NGR-tagged Rubredoxin to Act as a Cancer Therapeutic Drug" (2019). PCOM Biomedical Studies Student Scholarship. 164.