Activation of caspases-3, -6, and -9 during finasteride treatment of benign prostatic hyperplasia

J Clin Endocrinol Metab. 2005 Jan;90(1):17-25. doi: 10.1210/jcem.90.8.9993. Epub 2004 Oct 26.


Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5alpha-reductase such as finasteride have been shown to reduce the size of BPH tissues by inducing apoptosis, their mechanisms of action still remain unknown. The present study supports that such a process triggered by finasteride is caspase dependent with a possible involvement of two effector caspases (caspase-3 and 6) and two initiator caspases (caspase-8 and 9). Indeed, by using tissues from patients affected by BPH and treated by finasteride (5 mg/d) for 2-3, 6-8, or 27-32 d, we observed that the 5alpha-reductase inhibitor induced apoptosis in epithelial cells (evaluated through cell number positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) as early as 2-3 d of treatment, with a maximal activity (250-fold increase, P < 0.0001) at 6-8 d of treatment. However, after 27-32 d of treatment, the number of apoptotic cells was reduced and was close to control. Caspases-3, -6, -8, and -9 were immunolocalized to (basal and secretory) epithelial cells and to a lesser extent to stromal cells. Activated caspase-3 immunoexpression was restricted to epithelial secretory cells, and its immunostaining intensity appeared to be higher in BPH tissues from patients treated for 2-3 or 6-8 d. Consistently, in Western blotting analyses, activated caspases-3 and -6 were detected as early as 2-3 d of treatment in BPH tissues, and their levels were increased after 6-8 d of treatment. In real time quantitative PCR experiments, caspase-3 and -6 mRNA levels were found to be unchanged after finasteride treatment. Activated caspase-8 was not detected in the different conditions tested, whereas activated caspase-9 protein levels were maximally enhanced after 2-3 d of finasteride treatment. In conclusion, we report here that finasteride treatment of BPH tissues induced a caspase-dependent apoptotic process restricted to epithelial cells by activating effector caspases-3 and -6 and exhibited a transient action because the apoptotic process was no longer observed after 27-32 d of treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / drug effects
  • Caspase 3
  • Caspase 6
  • Caspase 9
  • Caspases / analysis*
  • Caspases / genetics
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Finasteride / pharmacology*
  • Finasteride / therapeutic use
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / enzymology
  • RNA, Messenger / analysis
  • Retrospective Studies


  • Enzyme Inhibitors
  • RNA, Messenger
  • Finasteride
  • CASP3 protein, human
  • CASP6 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 6
  • Caspase 9
  • Caspases