Ammonium-chloride-induced prostatic hypertrophy in vitro: urinary ammonia as a potential risk factor for benign prostatic hyperplasia

To test the possibility that urinary ammonia could be a risk factor for benign prostatic hyperplasia (BPH), we explored the cellular effects of ammonium chloride (NH₄Cl) on prostatic cancer cells used as an experimental model. Following treatment of human prostatic cancer DU-145 cells with the varying concentrations of NH₄Cl for 3 days, cell growth was inhibited by approximately 50% at 5 mM NH₄Cl and almost completely inhibited at 10 mM NH₄Cl. However, the individual cell size in these treated cells became approximately 2-fold larger and cellular protein content was also up to 2.5-fold greater than in untreated cells. This protein increase appeared to result from the reduced protein degradation, verified by metabolic labeling with [¹⁴C]valine. Western blot analysis further suggested that such reduced protein turnover could in part be due to the inactivation of a lysosomal acid protease, cathepsin D. Taken together, these studies demonstrate NH₄Cl-induced hypertrophy in prostatic cancer cells, as evidenced by the growth inhibition, cell enlargement, and cellular protein increase. Therefore, ammonia is not an inert metabolic product; instead, its chronic effects on the prostate may ultimately lead to significant cellular and biochemical alterations of the prostate such as BPH. Received: 27 June 1998 / Accepted: 25 March 1999