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Green tea polyphenols thwart prostate cancer development at multiple levels

Image: Green tea - just what the doctor orderedSchool of Medicine researcher Sanjay Gupta, Ph.D., assistant professor of urology, was part of the team behind a new study finding that a natural component of green tea targets molecular pathways that shut down prostate cancer proliferation and metastatic spread of tumor cells. They also found the tea component inhibits growth of tumor nurturing blood vessels. The study appears in the Dec. 1 issue of Cancer Research.

Gupta worked with researchers from the University of Wisconsin, Madison. They documented the role of green tea polyphenols (GTP) in modulating the insulin-like growth factor-1 (IGF-I)-driven molecular pathway in malignant prostate in a transgenic mouse model for human prostate cancer.

“Consumption of GTP led to reduced levels of IGF-I,”said Hasan Mukhtar, Ph.D., in the Department of Dermatology at the University of Wisconsin and the senior author of the paper. Mukhtar was a member of the Case dermatology department for several years, where he also conducted research on green tea. “GTP also led to increased levels of one of the binding proteins for IGF-I, the insulin growth factor binding protein-3. These observations bear significance in the light of studies that indicate increased levels of IGF-I is associated with increased risk of several cancers, such as prostate, breast, lung and colon.”

“Inhibition of the IGF-I axis could be a potential mechanism for prevention of prostate cancer,” Mukhtar said. “And natural components of green tea appear to interact with the molecular events that contribute to chemoprevention of those cancers.”

GTP modulation of cell growth via the IGF-I 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, and a hallmark of tumors is unregulated cell growth. GTP is capable of limiting the expression of these proteins in cancer cells, which could be in part inhibiting prostate cancer in this mouse model.

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

The green tea components 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-I levels. VEGF functions to recruit and develop new blood vessels that supply nutrients to developing tumors. By reducing the amount of VEGF, GTP works to minimize nutrients flowing to and supporting tumor growth and subsequent progression.

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

 

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