We recently reported that
angiotensin II receptor blockers (ARBs) have chemopreventive and chemotherapeutic potential against
prostate cancer via the reduction of
androgen receptor (AR) expression. In this study, we investigated the effects of the
angiotensin II receptor type 2 (AT2R) agonist
Compound 21 (
C21), which is expected to play similar roles to an ARB, on prostate
carcinogenesis using the transgenic rat for
adenocarcinoma of prostate (TRAP) model previously established in our laboratory. In vitro analyses of the cell growth, Western blotting and reporter gene assays were performed using LNCaP cells. TRAP rats at 6 weeks of age were randomly divided into 3 groups of 12 animals each and treated with
C21 at 1 or 2 mg/kg/day in
drinking water for 12 weeks.
C21 reduced the proliferation activity of
prostate cancer cells and down-regulated the PSA promoter activity and the AR
protein expression. We discovered that
C21 inhibited the progression of prostate
carcinogenesis in TRAP rats and decreased the incidence of
adenocarcinoma in the lateral prostate. A significant increase in the apoptotic index with activation of
caspase 3 and 7 were observed by immunohistochemistry and Western blotting analyses.
C21 also down-regulated the expression of AR significantly in TRAP rat prostate.
C21 decreased the expression of AR and reduced the proliferation activity effectively in
prostate cancer cells and TRAP rat prostate. These findings suggest that AT2R agonist may be a candidate novel chemopreventive agent against human
prostate cancer.