Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostate Carcinoma Cells
Abstract
-RICH OLIGONUCLEOTIDES (GROs) are a novel class of non-antisense nucleic acids that exhibit potent antiproliferative effects against malignant cells, including prostate cancer cells. The mechanism of GRG antiproliferative activity depends on their binding to nucleolin protein. Because they work by a novel mechanism (different from antisense oligonucleotides or traditional chemotherapy agents) and are expected to have few side effects, they have promise as new therapeutic agents for the treatment of prostate cancer. The major aims of this study were to test the efficacy of GROs in inhibiting the growth and metastasis of prostate cancer in rodent models, to investigate the mechanism of GROs, and to develop structural models of nucleolin for the development of new inhibitors. In the first year of this study, we have optimized GRO formulation and delivery in vitro and in vivo, and have been able to demonstrate impressive inhibitory effects against an aggressive hormone-independent tumor (DUl45) in mice We have also examined the effect of combined GRG and chemotherapy treatment on prostate cancer cells, and made considerable progress in developing a structural model of nucleolin. In summary, our results so far strongly support the potential of GROs as novel therapeutic agents for prostate cancer. Our work during this period has resulted in peer-reviewed publication and a patent filing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA406870
Entities
People
- Donald M. Miller
- John O. Trent
- Paula J. Bates
Organizations
- University of Louisville