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Grant Abstract

Grant Number: 1R21AT003397-01
PI Name: ROSELLI, CHARLES E.
Project Title: Saw Palmetto, Cyclooxygenase, and Prostate Cancer

Abstract: DESCRIPTION (provided by applicant): Phytotherapeutic formulations based on Saw Palmetto (Serenoa repens) are a traditional alternative therapy for the relief of lower urinary tract symptoms due to prostatic disease. The lipo-sterolic extract of saw palmetto (SPE) has been shown to be as effective as finasteride in the treatment of urinary symptoms from benign prostatic hyperplasia. SPE is one of the most commonly self-prescribed nutriceuticals used by patients with existing CaP in conjunction with conventional medical treatments however no data are available regarding its use for the treatment of prostate cancer (CaP) in men. It is generally agreed that cyclooxygenase-2 (COX-2) overexpression is associated with CaP and that selective inhibition of COX-2 may be useful for prevention and/or therapy of CaP. In vitro studies from our lab show that SPE inhibits the growth of human LnCaP cells, in part by inhibiting the expression of cyclooygenase-2 (COX-2) protein. Basal levels of COX-2 enzyme activity and protein expression are elevated in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, an animal model that exhibits molecular pathways of multistage prostate tumorigenesis. Treatment of TRAMP mice with a selective COX-2 inhibitor reduces CaP progression and metastases suggesting that COX-2 has a causative role for CaP development in this model. In contrast to recent reports of cardiotoxicity associated with selective COX-2 inhibitor drugs, SPE is well tolerated and has no significant toxicity. Thus, we propose to test the hypothesis that SPE can exert chemopreventative activity against CaP development and progression in TRAMP mice by inhibiting COX-2 activity and the production of prostaglandin E2. In addition, we will assess the effects of SPE on molecular targets in CaP linked to proliferation, inflammation, angiogenesis and invasiveness. The data from this study will contribute valuable information on whether SPE is an effective COX-2 inhibitor and test the popular notion that it has chemopreventative properties.

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