Effect of finasteride (Proscar) on the proliferation of cultured epithelial and stromal cells from normal and hyperplastic human prostates.
Finasteride is a potent 5 alpha-reductase inhibitor which has proven useful in the clinical management of benign prostatic hyperplasia. To determine a potential mode of action for finasteride in prostatic cell proliferation, we have studied the incorporation of [3H]-thymidine into the DNA of cultured epithelial and stromal cells from normal and hyperplastic human prostates. The effects of short treatment with 10(-9) M and 10(-6) M finasteride (48 hrs.) on the incorporation of labelled thymidine were studied. A significant effect of finasteride on prostatic cell proliferation was observed at 10(-6) M for both epithelium and stroma from normal prostate: the rate of thymidine incorporation decreased to 80 +/- 3% (p < 0.001) and 55 +/- 10% (p < 0.01), respectively, compared to the control cells. As observed for normal prostates, this rate of thymidine incorporation was less for hyperplastic epithelium (70 +/- 4%, p < 0.001) than that observed for the hyperplastic stroma (74 +/- 4%, p < 0.01). These data clearly demonstrate that the reduction of the prostate volume observed in BPH treatment by finasteride is partly due to an inhibition of cell proliferation. However, the absence of complete inhibition of cell proliferation at 10(-6) M, a concentration known to strongly inhibit the 5 alpha-reductase activity, supports the hypothesis that factors other than DHT are necessary to induce prostatic cell proliferation.
Lobaccaro
J M
JM
Institut National de la Santé et de la Recherche Médicale, INSERM Unité 439, Montpellier, France.
Boudon
C
C
Lechevallier
E
E
Mottet
N
N
Rebillard
X
X
Lumbroso
S
S
Gibelin
B
B
Sultan
C
C
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D018120:Finasteride / Q000494:pharmacology*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D014316:Tritium; D018120:Finasteride; D013936:Thymidine