Effects of Dutasteride on Prostate Carcinoma Primary Cultures: A Comparative Study With Finasteride and MK386

Purpose: The profound decrease in serum dihydrotestosterone observed with the dual 5?-reductase inhibitor dutasteride makes it an attractive agent for prostate cancer therapy. To our knowledge we compared for the first time the antitumor effect of dutasteride with that of the specific 5?-reductase-1 inhibitor MK386 and the specific 5?-reductase-2 inhibitor finasteride in human prostate primary cultures. Materials and Methods: Biochemical markers of the cellular response to 5?-reductase inhibitors were evaluated in primary cultures of prostate epithelial cancer cells from 54 patients with prostate carcinoma. Results: In our cohort of 54 patients prostate cancer cell growth decreased with dutasteride in 42 (about 78%), whereas in 21 (39%) it decreased with finasteride or MK386 alone. We observed a relationship between the levels of 5?-reductase enzymes in cell culture extracts and those revealed by immunohistochemistry in sections of samples from which we established primary cultures. Finasteride effects depended on 5?-reductase-2 levels and they were higher when the 5?-reductase-1:2 ratio was low. However, dutasteride effects were related to 5?-reductase-1 and 2 levels, and were not influenced by the 5?-reductase-1:2 ratio. Conversely the effects of MK386 were related to 5?-reductase-1 levels and they were higher when the 5?-reductase-1:2 ratio was high. Conclusions: Our data may provide a rationale for the use of a dual 5?-reductase inhibitor rather than a mono specific inhibitor for the prevention or treatment of early prostate cancer. This finding appears to confirm some preliminary clinical results and it could be due to the simultaneous presence of each 5?-reductase isoenzyme in prostate tumor cells.