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Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH)
Author(s) -
Quiles Maria T.,
Arbós Maria A.,
Fraga Antònia,
de Torres Inés M.,
Reventós Jaume,
Morote Juan
Publication year - 2010
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/pros.21138
Subject(s) - stromal cell , hyperplasia , prostate , cancer research , medicine , calponin , dihydrotestosterone , endocrinology , prostate cancer , apoptosis , androgen , chemistry , hormone , immunohistochemistry , cancer , biochemistry
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 = 3) and patients without benign prostatic hyperplasia (BPH) undergoing cystectomy (n = 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, α smooth muscle actin (αSMA), 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 17β‐estradiol (E2). RESULTS Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non‐BPH cells. Apoptosis targeted αSMA+ 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.