Dietary intake of many fruits and vegetables has been shown to be associated with reduced risk of
cancer. We investigated the in vivo efficacy of
grape seed extract (GSE, patented as Traconol) against
prostate cancer (PCA) and associated molecular events. Athymic nude mice were implanted with
hormone-refractory human prostate
carcinoma DU145 cells and fed with 100 and 200 mg/kg/day (5 days/week) doses of GSE for 7 weeks. At the end of experiment,
tumors were immunohistochemically analyzed for cell proliferation, apoptosis and angiogenesis. Our data show that GSE feeding strongly inhibited
tumor growth that accounted for 59-73% (p < 0.001) inhibition in
tumor volume and 37-47% (p < 0.05) decrease in
tumor weight at the end of the experiment. It did not show any significant change in
body weight gain profile and diet consumption. Immunohistochemical analysis of
tumors showed that GSE decreases proliferation index by 51-66% (p < 0.001) and increases apoptotic index by 3-4-fold (p < 0.001). CD31 staining for endothelial cells, showed decrease in intratumoral microvasculature in GSE-fed group of mice. Control
tumors showed 64.0 +/- 1.6 CD31 positive cells/400x field compared to 23.2 +/- 0.9 and 15.7 +/- 0.08 (p < 0.001) CD31 positive cells in 100 and 200 mg/kg doses of GSE-treated
tumors, respectively. GSE strongly inhibited (47-70%, p < 0.05)
vascular endothelial growth factor (
VEGF) secretion in
conditioned medium by DU145 cells. Recently, the circulating level of
insulin-like growth factor binding protein (IGFBP)-3 is shown to inversely related with PCA risk, growth and prognosis. Consistent with this, we observed 6-7-fold (p < 0.001) increase in
tumor-secreted levels of
IGFBP-3 after GSE feeding. In other immunohistochemical studies, compared to controls,
tumor xenografts from GSE-fed groups of mice showed a moderate decrease in
VEGF but an increase in
IGFBP-3 levels. These findings suggest that GSE possesses in vivo anticancer efficacy against
hormone-refractory human PCA, which is associated with its antiproliferative, proapoptotic and antiangiogenic activities together with upregulation of
IGFBP-3.