C W Bayne1, F Donnelly, M Ross, F K Habib. 1. Prostate Research Group, University Department of Oncology, Western General Hospital, Edinburgh, Scotland.
Abstract
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 5alpha-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 micrograms/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5alpha-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 5alpha-reductase isoenzyme activities in the prostate. Unlike other 5alpha-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. Copyright 1999 Wiley-Liss, Inc.
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 5alpha-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 micrograms/ml (calculated plasma concentration in patient receiving recommended therapeutic dosage) was shown to be an effective inhibitor of both 5alpha-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 5alpha-reductase isoenzyme activities in the prostate. Unlike other 5alpha-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. Copyright 1999 Wiley-Liss, Inc.
Authors: R Berges; K Dreikorn; K Höfner; S Madersbacher; M C Michel; R Muschter; M Oelke; O Reich; W Rulf; C Tschuschke; U Tunn Journal: Urologe A Date: 2009-12 Impact factor: 0.639