ANTIPROLIFERATIVE EFFECTS OF C-MYC ANTISENSE OLIGONUCLEOTIDE IN PROSTATE-CANCER CELLS - A NOVEL THERAPY IN PROSTATE-CANCER

Objectives. To explore the possibility of using antisense oligonucleot ide therapy for prostate cancer, we investigated the effect of c-myc-a ntisense-oligonucleotide (c-myc-As-ODN) in human prostate cancer,cell lines such as LNCaP, PC3, and DU145. Methods. LNCaP, PC3, and DU145 ce lls were incubated in the presence of c-myc-As-ODN. Dose (0 to 10 mu M ) and time dependent (1 to 6 days) effects on proliferation and viabil ity were examined by [H-3]thymidine incorporation and MTT assay, respe ctively. Flow cytometry analysis was carried out to analyze cell cycle status by determining the DNA content in LNCaP cells. Control culture s received either c-myc-sense-ODN or scrambled (nonsense) nucleotides. Results. Time-and dose-dependent decreases in DNA synthesis and cell viability were noted for all three prostate cancer cell lines after c- myc-As-ODN treatment. Further studies using LNCaP cells indicated that these changes were accompanied by an increase in the percentage of ce lls with less than 2N DNA content after c-myc-As-ODN treatment. The re sults suggest that c-myc-As-ODN induces cell death. Comparison of a c- myc-As-ODN-treated group with a group subjected to isoleucine deprivat ion revealed that thymidine incorporation was almost the same in c-myc -As-ODN-treated LNCaP cells and in LNCaP cells at early S phase. Concl usions. These results suggest that c-myc-As-ODN inhibits prostate canc er cell growth and proliferation mainly by decreasing cell viability. (C) 1997, Elsevier Science Inc. All rights reserved.