Antiproliferative effects of c-myc antisense oligonucleotide in prostate cancer cells: a novel therapy in prostate cancer.
OBJECTIVE
To explore the possibility of using antisense oligonucleotide therapy for prostate cancer, we investigated the effect of c-myc-antisense-oligonucleotide (c-myc-As-ODN) in human prostate cancer cell lines such as LNCaP, PC3, and DU145.


METHODS
LNCaP, PC3, and DU145 cells were incubated in the presence of c-myc-As-ODN. Dose (0 to 10 microM) and time dependent (1 to 6 days) effects on proliferation and viability were examined by [3H]thymidine incorporation and MTT assay, respectively. Flow cytometry analysis was carried out to analyze cell cycle status by determining the DNA content in LNCaP cells. Control cultures 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 cells with less than 2N DNA content after c-myc-As-ODN treatment. The results suggest that c-myc-As-ODN induces cell death. Comparison of a c-myc-As-ODN-treated group with a group subjected to isoleucine deprivation revealed that thymidine incorporation was almost the same in c-myc-As-ODN-treated LNCaP cells and in LNCaP cells at early S phase.


CONCLUSIONS
These results suggest that c-myc-As-ODN inhibits prostate cancer cell growth and proliferation mainly by decreasing cell viability.
Balaji
K C
KC
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655, USA.
Koul
H
H
Mitra
S
S
Maramag
C
C
Reddy
P
P
Menon
M
M
Malhotra
R K
RK
Laxmanan
S
S
D000704:Analysis of Variance; D001345:Autoradiography / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry / Q000379:methods; D016259:Genes, myc; D006801:Humans; D008297:Male; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense