Chemopreventive effect of cinnamon and its bioactive compounds in a rat model of premalignant prostate carcinogenesis


 Cinnamon and its bioactive compounds inhibit prostate cancer cell proliferation in vitro. The aim of the present study was to assess the chemopreventive efficacy of cinnamon (CN) and its bioactive compounds in vivo using N-methyl-N-nitrosourea [MNU] and testosterone [T] to induce prostate carcinogenesis in male Wistar/NIN rats. Cancer-induced (CI) rats (n=10) developed prostatic hyperplasia and prostatic intraepithelial neoplasia (PIN). These histopathological changes were diminished in CI rats fed for four months with diets supplemented with either CN (n=20) or its bioactive compounds (cinnamaldehyde, n=10 and procyanidin B2, n=10). Androgen receptor (AR) expression was lower in the prostates of CI rats than in control, but the AR target gene, probasin, was robustly upregulated. Treatment of CI rats with CN or its bioactive compounds upregulated AR expression but inhibited the expression of the 5 alpha reductase genes (SRD5a1 and SRD5a2) and did not further increase probasin expression, suggesting blunted transcriptional activity of AR due to the limited availability of dihydrotestosterone. MNU+T induced an altered oxidant status in rat prostate, which was reflected by an increase in lipid peroxidation and DNA oxidation. These changes were completely or partially corrected by treatment with CN or the bioactive compounds. CN and its active components increased the activity of the apoptotic enzymes caspase 8 and caspase 3 in the prostates of CI rats. In conclusion, our data demonstrate that CN and its bioactive compounds have inhibitory effects on premalignant prostate lesions induced by MNU+T and, therefore, may be considered for the chemoprevention of prostate cancer.