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Serenoa repens (Permixon ® ): A 5α‐reductase types I and II inhibitor—new evidence in a coculture model of BPH
Author(s) -
Bayne Colin W.,
Donnelly Frank,
Ross Margaret,
Habib Fouad K.
Publication year - 1999
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19990901)40:4<232::aid-pros4>3.0.co;2-0
Subject(s) - prostate , prostate cancer , medicine , intracellular , cancer research , pharmacology , cancer , biochemistry , chemistry
BACKGROUND The aim of this study was to determine the effect of the phytotherapeutic agent, Permixon ® , on a novel coculture model of benign prostatic hyperplasia (BPH) in an effort to better understand the mode of action of the drug in vivo. METHODS The effect of Permixon ® , at the calculated therapeutic concentration, on the activity of 5α‐reductase isoenzymes was evaluated utilizing a pH‐specific assay. Prostate‐specific antigen (PSA) secretions into the medium were measured in the presence and absence of Permixon ® and quantified by an ELISA assay. The morphological patterns before and following Permixon ® treatment were also examined by electron microscopy. All results were compared to controls. RESULTS Permixon ® at a concentration of 10 μg/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5α‐reductase types I and II isoenzymes without influencing the secretion of PSA by the epithelial cells, even after stimulation with testosterone. The morphology of Permixon ® ‐treated cells was found to be markedly different from that of untreated controls. Cells which had been treated with the drug demonstrated extensive accumulation of lipids in the cytoplasm and widespread damage of intracellular membranes, including mitochondrial and nuclear membranes. CONCLUSIONS Permixon ® is an effective dual inhibitor of 5α‐reductase isoenzyme activities in the prostate. Unlike other 5α‐reductase inhibitors, Permixon ® induces this effect without interfering with the cells' capacity to secrete PSA, thus permitting the continued use of PSA measurements for prostate cancer screening. Prostate 40:232–241, 1999. © 1999 Wiley‐Liss, Inc.