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Green Tea Polyphenols Thwart Prostate Cancer Development at Multiple Levels

By American Association for Cancer Research*

PHILADELPHIA – The polyphenols present in green tea help prevent the spread of prostate cancer by targeting molecular pathways that shut down the proliferation and spread of tumor cells, as well as inhibiting the growth of tumor nurturing blood vessels, according to research published in the December 1 issue of Cancer Research.

A team of researchers from the University of Wisconsin, Madison, Wis., and Case Western Reserve University, Cleveland, Ohio, documented the role of green tea polyphenols (GTP) in modulating the insulin-like growth factor-1 (IGF-1)-driven molecular pathway in prostate tumor cells in a mouse model for human prostate cancer.

“Consumption of GTP led to reduced levels of IGF-1,” said Hasan Mukhtar, Ph.D., Department of Dermatology at the University of Wisconsin, the senior author of the paper.

“GTP also led to increased levels of one of the binding proteins for IGF-1, the insulin growth factor binding protein-3. These observations bear significance in light of studies that indicate increased levels of IGF-1 are associated with increased risk of several cancers, such as prostate, breast, lung and colon.”

GTP modulation of cell growth via the IGF-1 axis coincides with limited production or phosphorylation of key cell survival proteins, including PI3K, Akt and Erk1/2, the research indicated. The PI3K molecular pathway in cells, which includes Akt and Erk1/2, works to promote cell survival, rather than programmed cell death, also known as apoptosis.

GTP also caused reduced expression of proteins known to be associated with the metastatic spread of cancer cells. GTP inhibited the levels of urokinase plasminogen activator as well as matrix metalloproteinases 2 and 9, cellular molecules linked to the metastasis.

The green tea polyphenols contributed to minimizing tumor development by governing the amount of vascular endothelial growth factor (VEGF) in the serum of the prostate cancer mouse model. The reduction of VEGF may result from GTP-induced suppression of IGF-1 levels. VEGF functions to recruit and develop new blood vessels that carry nutrients to developing tumors. By reducing the amount of VEGF, GTP works to minimize nutrients flowing to and supporting tumor growth.

Mukhtar’s colleagues contributing to the study included Vaqar Mustafa Adhami, Imtiaz Ahmad Siddiqui, and Nihal Ahmad from the University of Wisconsin; and Sanjay Gupta from Case Western Reserve University.

Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis and upregulates insulin-like growth factor binding protein-3.

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.

PMID: 14696100 [PubMed - indexed for MEDLINE]

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