Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).
BACKGROUND
Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model.


METHODS
Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis.


RESULTS
Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence.


CONCLUSIONS
Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance.
Wadsworth
Teri L
TL
Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Worstell
Teresa R
TR
Greenberg
Norman M
NM
Roselli
Charles E
CE
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D013196:Dihydrotestosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D028024:Serenoa / Q000737:chemistry*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C040972:saw palmetto extract