Activation of Caspases-3, -6, and -9 During Finasteride Treatment of Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) results from an increase in both epithelial and stromal compartments of the human prostate. Although inhibitors of 5α-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 5α-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 apoptoti...