Lovastatin-induced apoptosis in prostate stromal cells

Area of Science:

• Urology
• Cell Biology
• Pharmacology

Background:

• Benign prostatic hyperplasia (BPH) is a prevalent condition in aging men, often inadequately managed by current medical treatments, necessitating surgical intervention for symptom relief.
• BPH is characterized by an increase in prostate epithelial and stromal cells, with stromal cells being particularly implicated due to their longevity and resistance to androgen withdrawal.

Purpose of the Study:

• To investigate the feasibility of pharmacologically inducing apoptosis in cultured benign prostatic hyperplasia (BPH) stromal cells.
• To explore the effects of lovastatin, a HMGCoA reductase inhibitor, and its related metabolites on BPH stromal cell apoptosis.

Main Methods:

• Benign prostatic hyperplasia (BPH) stromal cells were isolated from surgical tissue and cultured.
• Apoptosis was induced using lovastatin (30 micromol/L) and its effects were analyzed in the presence of androgens (testosterone, DHT, finasteride) and cholesterol pathway metabolites.
• Apoptosis was confirmed through DNA laddering, acridine orange staining, and flow cytometry.

Main Results:

• Lovastatin at 30 micromol/L significantly induced apoptosis in BPH stromal cells (16.6% vs. 2.5% in control).
• Lovastatin-induced apoptosis was not influenced by androgen withdrawal or stimulation (testosterone, DHT, finasteride).
• Mevalonic acid and geranyl geraniol inhibited lovastatin-induced apoptosis, while farnesol, squalene, and 7-ketocholesterol did not.

Conclusions:

• Lovastatin effectively induces apoptosis in benign prostatic hyperplasia (BPH) stromal cells in vitro, independent of androgenic influences.
• While lovastatin itself may not be a direct in vivo treatment for BPH, it serves as a valuable tool for inducing apoptosis in experimental settings.
• Further understanding of the apoptotic pathways in BPH stromal cells could pave the way for novel therapeutic strategies for BPH.