Prostate cancer, the most prevalent non-cutaneous
cancer in men, is associated with increased age. This suggests that dietary chemopreventive measures could be effective in delaying the onset or decreasing the severity of the disease. We utilized the Lobund-Wistar rat
nitrosomethylurea induced,
testosterone promoted (NMU-T) model of male sex accessory gland
cancer to test the potential chemopreventive effects of myo-
inositol and
limonene on
tumor incidence and associated
protease activities.
Tumors were found to arise in the seminal vesicles and dorsal and anterior prostate lobes. There were also some
tumors that appeared to arise in both the seminal vesicles and anterior prostate, and in some cases the tissue of origin was not clear. The distribution of
tumors as to site of origin in
limonene or myo-
inositol treated animals did not vary from that of the
starch fed control animals, and the number of animals presenting with
metastases did not vary significantly between treatment groups. There was a statistically significant delay in onset of
tumors in myo-
inositol, but not
limonene fed rats,
at 10 months post-induction of
carcinogenesis; however, at 12 and 15 months this was not significant. The ventral prostate and seminal vesicles expressed
pro-MMP-2 and
plasminogen activator (PA) activities. Based on sensitivity to
amiloride, the PA activities were predominately
urokinase (uPA) in the ventral prostate and a mixture of tissue-type activator (tPA) and uPA in the seminal vesicles of non-treated rats. Sex accessory gland
tumors, and
metastases, expressed increased levels PA and pro- and active forms of MMP-2 and -9. The PA activities of the
tumors were a mixture of uPA and tPA. There was no difference in the levels of these
protease activities based on the tissue of
tumor origin, nor in
tumor vs
metastasis. These studies indicate that
MMP and PA activities play a role in sex accessory gland
tumor biology and that dietary supplementation with myo-
inositol can delay but not ultimately prevent the development of such
tumors.