Multitargeted therapy of cancer by ellagitannins.

Ellagitannins are bioactive polyphenols that have antioxidant and anti-inflammatory bioactivities. Pomegranate juice has the highest concentration of ellagitannins of any commonly consumed juice and contains the unique ellagitannin, punicalagin. Punicalagin is the largest molecular weight polyphenol known. Ellagitannins are not absorbed intact into the blood stream but are hydrolyzed to ellagic acid. They are also metabolized by gut flora into urolithins which are conjugated in the liver and excreted in the urine. These urolithins are also bioactive and inhibit prostate cancer cell growth. Inhibition of Nuclear Factor Kappa-B activation has been shown in prostate cancer cells and in human prostate cancer xenografts in mice. In clinical studies, pomegranate juice administration led to a decrease in the rate of rise of Prostate Specific Antigen after primary treatment with surgery or radiation. Continued translational research on the chemopreventive potential of pomegranate ellagitannins is ongoing.