The Potential for Ruthenium-Substituted Rubredoxin with Attached Tumor-Homing Peptide NGR as a Selective Cancer Therapeutic Drug
Start Date
10-5-2016 1:00 PM
Description
The difficulty in discerning the exact causes of cancer is reflected in the inability to find a truly selective cancer treatment. Many unpleasant side effects of modern treatments are due to lack of selectivity. The utility of recent, more selective cancer treatments is squandered by their lack of generalizability to diverse cancer phenotypes. Currently, tumor-homing peptides and tumor-penetrating peptides are being studied in an effort to increase the selectivity and delivery of anti-cancer compounds. The non-heme iron-containing redox protein, rubredoxin, from the hyperthermophilic archaeon Pyrococcus furiosus is of particular interest due to its thermostability, ease of modification, solubility, and its lack of immunogenicity. Past research has shown rubredoxin’s ability to be mutated to express a tumor-homing peptide and to substitute its natural iron center with other metals. The present study demonstrates the ability to attach a tumor homing peptide containing the NGR motif to rubredoxin and the selectivity of the NGR peptide-tagged Ru-substituted rubredoxin for the human fibrosarcoma cell line (HT1080). We further show preliminary evidence of cytotoxicity in the HT1080 cell line. This study also aims to further demonstrate the specificity of this treatment by comparison of its cytotoxic effects between the HT1080 and MCF10a cell lines as well as a comparison with the effects of doxorubicin, a popular chemotherapeutic agent.
The Potential for Ruthenium-Substituted Rubredoxin with Attached Tumor-Homing Peptide NGR as a Selective Cancer Therapeutic Drug
The difficulty in discerning the exact causes of cancer is reflected in the inability to find a truly selective cancer treatment. Many unpleasant side effects of modern treatments are due to lack of selectivity. The utility of recent, more selective cancer treatments is squandered by their lack of generalizability to diverse cancer phenotypes. Currently, tumor-homing peptides and tumor-penetrating peptides are being studied in an effort to increase the selectivity and delivery of anti-cancer compounds. The non-heme iron-containing redox protein, rubredoxin, from the hyperthermophilic archaeon Pyrococcus furiosus is of particular interest due to its thermostability, ease of modification, solubility, and its lack of immunogenicity. Past research has shown rubredoxin’s ability to be mutated to express a tumor-homing peptide and to substitute its natural iron center with other metals. The present study demonstrates the ability to attach a tumor homing peptide containing the NGR motif to rubredoxin and the selectivity of the NGR peptide-tagged Ru-substituted rubredoxin for the human fibrosarcoma cell line (HT1080). We further show preliminary evidence of cytotoxicity in the HT1080 cell line. This study also aims to further demonstrate the specificity of this treatment by comparison of its cytotoxic effects between the HT1080 and MCF10a cell lines as well as a comparison with the effects of doxorubicin, a popular chemotherapeutic agent.