Colon cancer chemopreventive activities of pomegranate ellagitannins and urolithins.

Pomegranate juice derived ellagitannins and their intestinal bacterial metabolites, urolithins, inhibited TCDD-induced CYP1-mediated EROD activity in vitro with IC(50) values ranging from 56.7 microM for urolithin A to 74.8 microM for urolithin C. These compounds exhibited dose- and time-dependent decreases in cell proliferation and clonogenic efficiency of HT-29 cells. Inhibition of cell proliferation was mediated through cell cycle arrest in the G(0)/G(1) and G(2)/M stages of the cell cycle followed by induction of apoptosis. These results indicate that the ellagitannins and urolithins released in the colon upon consumption of pomegranate juice in considerable amounts could potentially curtail the risk of colon cancer development, by inhibiting cell proliferation and inducing apoptosis.