Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH).
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, alpha smooth muscle actin (alphaSMA), 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 17beta-estradiol (E2).


RESULTS
Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non-BPH cells. Apoptosis targeted alphaSMA+ 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.
Quiles
Maria T
MT
Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain. mtquiles@ir.vhebron.net
Arbós
Maria A
MA
Fraga
Antònia
A
de Torres
Inés M
IM
Reventós
Jaume
J
Morote
Juan
J
D000199:Actins / Q000378:metabolism; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D008517:Phytotherapy / Q000379:methods*; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D000068218:Prunus africana / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D010936:Plant Extracts; C100762:SMTN protein, human; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D016222:Fibroblast Growth Factor 2