Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts.
The effect of a Pygeum africanum extract (Tadenan) (Pa), used in the treatment of micturition disorders associated with BPH, has been examined on the proliferation of rat prostatic stromal cells stimulated by different growth factors. EGF, bFGF, and IGF-I but not KGF are mitogenic for prostatic fibroblasts in culture. Pygeum africanum inhibits both basal and stimulated growth with IC50 values of 4.5, 7.7 and 12.6 micrograms./ml. for EGF, IGF-I and bFGF, respectively, compared to 14.4 micrograms./ml. for untreated cells, the inhibition being stronger towards EGF. Pygeum africanum inhibited the proliferation induced by TPA or PDBu in a concentration-dependent manner with IC50 values of 12.4 and 8.1 micrograms./ml. respectively. The antiproliferative effects of Pa were not ascribed to cytotoxicity. These results show that Pygeum africanum is a potent inhibitor of rat prostatic fibroblast proliferation in response to direct activators of protein kinase C, the defined growth factors bFGF, EGF and IGF-I, and the complex mixture of mitogens in serum depending on the concentration used. PKC activation appears to be an important growth factor-mediated signal transduction for this agent. These data suggest that therapeutic effect of Pygeum africanum may be due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man.
Yablonsky
F
F
Laboratoires Debat, groupe Fournier, Garches, France.
Nicolas
V
V
Riffaud
J P
JP
Bellamy
F
F
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010936:Plant Extracts; D011467:Prostate / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D005233:Fatty Alcohols; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D010936:Plant Extracts; C009375:Tadenan; D016222:Fibroblast Growth Factor 2; D051523:Fibroblast Growth Factor 7; D015240:Phorbol 12,13-Dibutyrate; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D013755:Tetradecanoylphorbol Acetate