Chemoprevention of Prostate Carcinogenesis by DFMO and/or Finasteride Treatment in Male Wistar Rats

Abstract

In the present study the chemopreventive activities of DFMO, the irreversible inhibitor of ornithine decarboxylase, and finasteride, the inhibitor of prostatic 5a-reductase, against the development of chemically induced prostate adenocarcinoma by methylnitrosourea/testosterone propionate in male Wistar rats were investigated. According to histological examination, oral administration of DFMO and finasteride, either alone or combined, for two months to MNU/TP-inoculated rats reduced the tumor incidence to 11.11%, 10% and 10%, respectively, compared to tumored controls (64.3%). DFMO and/or finasteride treatment resulted in significant reductions in the wet weight of the prostate gland and seminal vesicles and its ratio relative to the total body weight, as well as the levels of prostate total protein, DNA, RNA and DNA/RNA ratio, compared to tumored controls. However, the effect of the combined treatment was of no statistical significance compared to single DFMO or finasteride treatment, as demonstrated by the non-significant differences between the mean values of most of the studied parameters. The tumor chemopreventive activity and the prostate growth inhibitory effect of DFMO and finasteride were due to suppression of prostate polyamine synthesis. ANOVA test revealed that the relative weight of the prostate as well as blood and tissue polyamine levels could be used as significant endpoint biomarkers for DFMO and finasteride as cancer chemopreventive agents.