EFFECT OF THE LIPIDOSTEROLIC EXTRACT OF SERENOA REPENS(PERMIXON(R)) 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 Seren oa repens (LSESr) on in vitro cell proliferation in biopsies of human prostate Material and Methods: Cell proliferation was assessed by inco rporation of [H-3]thymidine followed by historadiography. Results: Bas ic 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 th e other regions of the prostate. Similar results were observed with ep idermal growth factor (EGF), although the increase in cell proliferati on was not recorded in some cases. Lovastatin, an inhibitor of hydroxy methylglutaryl coenzyme A, antagonized both the basal proliferation an d the growth factor-stimulated proliferation of human prostate epithel ium (EGF, mean inhibition approximate to 80-95%; b-FGF, mean inhibitio n approximate to 40-90%). Geraniol, a precursor of both farnesyl pyrop hosphate 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 p roliferation was observed with the highest concentration of LSESr (30 mu g/ml). In contrast, LSESr inhibited b-FGF-induced proliferation of human prostate cell cultures; this effect was significant for the high est concentration of LSESr (30 mu g/ml). In some prostate samples, a s imilar inhibition was also noted with lower concentrations. Unsaturate d fatty acids (UFA), in the range 1-30 ng/ml, did not affect the basal prostate cell proliferation, only a slight increase in cell prolifera tion was noted in 1 prostate specimen. UFA(1, 10 or 30 mu g/ml) marked ly inhibited the b-FGF-induced cell proliferation down to the basal va lue. Lupenone, hexacosanol and the unsaponified fraction of LSESr mark edly inhibited the b-FGF-induced cell proliferation, whereas a minimal effect on basal cell proliferation was noted. Conclusions: Despite th e large variability in the response of the prostate samples to b-FGF, these results indicate that LSESr and its components affect the prolif erative response of prostate cells to b-FGF more than their basal prol iferation.