Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies.
OBJECTIVE
To assess the effect of the lipidosterolic extract of Serenoa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate


METHODS
Cell proliferation was assessed by incorporation of [3H]thymidine followed by historadiography.


RESULTS
Basic fibroblast growth factor (b-FGF) induced a considerable increase in human prostate cell proliferation (from +100 to +250%); the glandular epithelium was mainly affected, minimal labeling being recorded in the other regions of the prostate. Similar results were observed with epidermal growth factor (EGF), although the increase in cell proliferation was not recorded in some cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A, antagonized both the basal proliferation and the growth factor-stimulated proliferation of human prostate epithelium (EGF, mean inhibition approximately 80-95%; b-FGF, mean inhibition approximately 40-90%). Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate, increased cell proliferation only in some prostate specimens, this effect being antagonized by lovastatin. LSESr did not affect basal prostate cell proliferation, with the exception of two prostate specimens in which a significant inhibition of basal proliferation was observed with the highest concentration of LSESr (30 micrograms/ ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the highest concentration of LSESr (30 micrograms/ml). In some prostate samples, a similar inhibition was also noted with lower concentrations. Unsaturated fatty acids (UFA), in the range 1-30 ng/ml), did not affect the basal prostate cell proliferation, only a slight increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10 or 30 micrograms/ml) markedly inhibited the b-FGF-induced cell proliferation down to the basal value. Lupenone, hexacosanol and the unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted.


CONCLUSIONS
Despite the large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the proliferative response of prostate cells to b-FGF more than their basal proliferation.
Paubert-Braquet
M
M
Bio-Inova Euro Lab Research Laboratories, Plaisir, France.
Cousse
H
H
Raynaud
J P
JP
Mencia-Huerta
J M
JM
Braquet
P
P
D000080462:Acyclic Monoterpenes; D000726:Androgen Antagonists / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005204:Farnesol / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000473:pathology; D028024:Serenoa; D013729:Terpenes / Q000494:pharmacology
D000080462:Acyclic Monoterpenes; D000726:Androgen Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010936:Plant Extracts; D013729:Terpenes; D016222:Fibroblast Growth Factor 2; D005204:Farnesol; D004815:Epidermal Growth Factor; D008148:Lovastatin; C040972:saw palmetto extract; C007836:geraniol