Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostatic Carcinoma Cells
Abstract
This proposal was based on our original observation that certain G-rich oligonucleotides (GROs) inhibited the growth of cultured prostate cancer cells. The sequences of the active oligonucleotides led us to hypothesize that GROs could form G-quartet containing structures that bind to specific cellular proteins. The overall goal of this proposal was to characterize the structure and mechanism of these novel oligonucleotides. In the first half of this study, the hypotheses regarding G-quartet formation and protein binding were confirmed, and a protein called nucleolin was identified as the tentative target of GROs. During the current reporting period, we have completed the remaining studies in the Phase I proposal. Key results in this period include the following: (1) Structure determination of an active GRO by molecular modeling supported by biophysical data, (2) Demonstration of apoptosis induction in GRO-treated prostate cancer cells, (3) Confirmation of nucleolin as a GRO binding protein and extension of the correlation between GRO activity and ability to bind to nucleolin, and (4) Completion of TRAP assays showing the inability of GROs to inhibit telomerase. In summary, all of the studies proposed in Phase I have been successfully completed or addressed by alternative approaches. This study has produced considerable data to support GROs as potential therapeutic agents for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA407225
Entities
People
- Donald M. Miller
- John O. Trent
- Paula J. Bates
Organizations
- University of Louisville