| Prostate cancer is the most common type diagnosed among men in the United States. Random oligodeoxynucleotide (ODN) libraries are used to generate DNA aptamers by systematic evolution of ligands by exponential enrichment (SELEX). We explored the utility of guanine-rich libraries, and found that some had cancer-selective antiproliferative activity that generally correlated with G-quadruplex formation, nuclease resistance, and enhanced cellular uptake. We identified several proteins by mass spectrometry that bind to GC and cytosine ODNs. We compared the GT library with the classic random library for SELEX of whole prostate cancer cells and identified a new aptamer from the GT library with enhanced nuclease resistance and antiproliferative activity. We present evidence that AS1411, a known G-rich anticancer aptamer, inhibits prostate tumor initiating cells. This body of work supports the hypothesis that G-rich ODNs are well suited to the development of new aptamers in the treatment of cancer. |
