TheProstate70:1044^1053(2010) AntiproliferativeandApoptoticEffectsoftheHerbal Agent Pygeum africanum onCulturedProstateStromal Cells From PatientsWith Benign Prostatic Hyperplasia (BPH) Maria T. Quiles, 1 * Maria A. Arbo ´s, 1 Anto ` nia Fraga, 1 Ine ´s M. de Torres, 2 Jaume Revento ´s, 1 and Juan Morote 3 1 Institutde Recerca,Hospital Universitari Valld’Hebron,Universitat Auto' nomade Barcelona,Barcelona,Spain 2 Departmentof Pathology,Hospital Universitari Valld’Hebron,Universitat Auto' nomade Barcelona,Barcelona,Spain 3 Departmentof Urology,Hospital Universitari Valld’Hebron,Universitat Auto' nomade Barcelona,Barcelona,Spain BACKGROUND. Previous reports show that the herbal agent Pygeum africanum (PA) used to treat benign prostatic hyperplasia (BPH) inhibits proliferation of prostate stromal cells from BPH tissues. To determine underlying mechanisms, we compared proliferative and apoptotic responses to PA between BPH and non-BPH prostate stromal cells with a focus on the specific reaction displayed by stromal cell subsets. An interaction of PA with growth factors and hormones was also investigated. METHODS. Primary prostate stromal cells from BPH/LUTS patients undergoing open prostatectomy (n ¼ 3) and patients without benign prostatic hyperplasia (BPH) undergoing cystectomy (n ¼ 3) were treated with PA. Cells were characterized by immunofluorescence. Sensitivity to PA was determined using proliferation assays. Apoptosis, transforming growth factor B1 (TGFB1), fibroblast growth factor 2 (FGF2), vimentin, a smooth muscle actin (aSMA), and smoothelin expression were examined after PA treatment. Cell immunophenotype and proliferation were tested after incubating cells with PA plus either FGF2, TGFB1, vascular endothelial growth factor (VEGF), dihydrotestosterone (DHT) or 17b-estradiol (E2). RESULTS. Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non-BPH cells. Apoptosis targeted aSMAþ cells, more abundant in BPH cells. Downregulation of TGFB1 expression was induced by PA. FGF2 increased cells sensitivity to PA. Incubation with other mitogenic factors like VEGF, DHT, and E2 decreased sensitivity to PA. Both TGFB1 and E2 blocked the antiproliferative activity of PA. CONCLUSIONS. Results suggest that PA is antiproliferative and apoptotic on proliferative prostate fibroblasts and myofibroblasts but not on smooth muscle cells. Mechanisms of action include TGFB1 downregulation and inhibition of FGF2 specific signaling. Prostate 70: 1044– 1053, 2010. # 2010 Wiley-Liss, Inc. KEY WORDS: myofibroblast; reactive stroma; smooth-muscle cell; phytotherapy; growth factors and hormones Additional Supporting Information may be found in the online version of this article. Maite Quiles and Maria A. Arbo ´ s contributed equally to this work. None of the contributing authors have any conflicts of interest. Grant sponsor: Elfar-Drag (Madrid, Spain); Grant sponsor: Instituto Carlos III, Ministerio de Ciencia e Innovacio ´ n, Spain; Grant number: RTICC RD06/0020/0058; Grant sponsor: Departament de Universi- tats, Recerca i Societat de la Informacio, Generalitat de Catalunya, Spain; Grant number: 2005SGR00553. *Correspondence to: Maria T. Quiles, PhD, Institut de Recerca, Hospital Universitari Vall d’Hebron, Pg. Vall d’Hebron 119-139, 08035 Barcelona, Spain. E-mail: mtquiles@ir.vhebron.net Received 20 November 2009; Accepted 6 January 2010 DOI 10.1002/pros.21138 Published online 5 April 2010 in Wiley InterScience (www.interscience.wiley.com). ß2010Wiley-Liss,Inc.