Serenoa repens (Permixon (R)): A 5 alpha-reductase types I and II inhibitor - New evidence in a coculture model of BPH

BACKGROUND. The aim of this study was to determine the effect of the phytot herapeutic agent, Permixon(R), on a novel coculture model of benign prostat ic hyperplasia (BPH) in an effort to better understand the mode of action o f the drug in vivo. METHODS. The effect of Permixon(R), at the calculated therapeutic concentra tion, on the activity of 5 alpha-reductase isoenzymes was evaluated utilizi ng a pH-specific assay. Prostate-specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon(R) and quanti fied by an ELISA assay. The morphological patterns before and following Per mixon(R) treatment were also examined by electron microscopy. All results w ere compared to controls. RESULTS. Permixon(R) at a concentration of 10 mu g/ml (calculated plasma co ncentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5 alpha-reductase types I and II isoen zymes without influencing the secretion of PSA by the epithelial cells, eve n after stimulation with testosterone. The morphology of Permixon(R)-treate d cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumula tion of lipids in the cytoplasm and widespread damage of intracellular memb ranes, including mitochondrial and nuclear membranes. CONCLUSIONS. Permixon(R) is an effective dual inhibitor of 5 alpha-reductas e isoenzyme activities in the prostate. Unlike other 5 alpha-reductase inhi bitors, Permixon(R) induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurem ents for prostate cancer screening. (C) 1999 Wiley-Liss, Inc.