Study Title:

Green Tea, Red Wine & Prostate Cancer

Study Abstract

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway has been associated with cancer promotion and progression and resistance to treatments in a number of cancers, including prostate adenocarcinoma. Here we provide the first evidence that dietary agents, namely, epigallocatechin gallate (EGCg, IC5075 μM), resveratrol (IC5040 μM), or a mixture of polyphenols from green tea [polyphenon E (PPE), IC5070 μM] or grapevine extract (vineatrol, IC5030 μM), impede prostate cancer cell growth in vitro and in vivo by inhibiting the SphK1/S1P pathway. We establish that SphK1 is a downstream effector of the ERK/phospholipase D (PLD) pathway, which is inhibited by green tea and wine polyphenols. Enforced expression of SphK1 impaired the ability of green tea and wine polyphenols, as well as pharmacological inhibitors of PLD and ERK activities, to induce apoptosis in PC-3 and C4-2B cells. The therapeutic efficacy of these polyphenols on tumor growth and the SphK1/S1P pathway were confirmed in animals using a heterotopic PC-3 tumor in place model. PC-3/SphK1 cells implanted in animals developed larger tumors and resistance to treatment with polyphenols. Furthermore, using an orthotopic PC-3/GFP model, the chemopreventive effect of an EGCg or PPE diet was associated with SphK1 inhibition, a decrease in primary tumor volume, and occurrence and number of metastases. These results provide the first demonstration that the prosurvival, antiapoptotic SphK1/S1P pathway represents a target of dietary green tea and wine polyphenols in cancer.

From press release:

In what could lead to a major advance in the treatment of prostate cancer, scientists now know exactly why polyphenols in red wine and green tea inhibit cancer growth. This new discovery, published online in The FASEB Journal, explains how antioxidants in red wine and green tea produce a combined effect to disrupt an important cell signaling pathway necessary for prostate cancer growth. This finding is important because it may lead to the development of drugs that could stop or slow cancer progression, or improve current treatments.

"Not only does SphK1/S1P signaling pathway play a role in prostate cancer, but it also plays a role in other cancers, such as colon cancer, breast cancer, and gastric cancers," said Gerald Weissmann, MD, editor-in-chief of The FASEB Journal. "Even if future studies show that drinking red wine and green tea isn't as effective in humans as we hope, knowing that the compounds in those drinks disrupts this pathway is an important step toward developing drugs that hit the same target."

Scientists conducted in vitro experiments which showed that the inhibition of the sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway was essential for green tea and wine polyphenols to kill prostate cancer cells. Next, mice genetically altered to develop a human prostate cancer tumor were either treated or not treated with green tea and wine polyphenols. The treated mice showed reduced tumor growth as a result of the inhibited SphK1/S1P pathway. To mimic the preventive effects of polyphenols, another experiment used three groups of mice given drinking water, drinking water with a green tea compound known as EGCg, or drinking water with a different green tea compound, polyphenon E. Human prostate cancer cells were implanted in the mice and results showed a dramatic decrease in tumor size in the mice drinking the EGCg or polyphenon E mixtures.

"The profound impact that the antioxidants in red wine and green tea have on our bodies is more than anyone would have dreamt just 25 years ago," Weissmann added. "As long as they are taken in moderation, all signs show that red wine and green tea may be ranked among the most potent 'health foods' we know."

Study Information

1.L. Brizuela, A. Dayon, N. Doumerc, I. Ader, M. Golzio, J.-C. Izard, Y. Hara, B. Malavaud, O. Cuvillier.
The sphingosine kinase-1 survival pathway is a molecular target for the tumor-suppressive tea and wine polyphenols in prostate cancer.
The FASEB Journal
2010 June

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