Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostatic Carcinoma Cells.

We have discovered that certain G-rich oligonucleotides GROs can have potent antiproliferative activity against prostate cancer cells in vitro. We had previously shown that growth inhibitory GROs formed specific complexes with nuclear proteins more readily than inactive GROs. Our hypotheses are that the active GROs form structures containing G-quartets, that these structures are recognized by specific cellular proteins, and that binding to these proteins is involved in the growth inhibitory effects. Our overall aims are to assess the specificity of the antiproliferative effects, characterize the structure of GROs, identify GRO-binding proteins, and to design more active GROs by rational and combinatorial methods. A greater understanding of the mechanism of the antiproliferative effects may lead to the identification of new targets and improved therapies for the treatment of prostate cancer. We have now substantially improved our understanding of the growth inhibitory effects. Most significantly, we have now identified a GRO-binding protein, and shown that ability of GROs to bind this protein corresponds to their antiproliferative activity.