IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid

Altered cell and tissue differentiation is characteristic of premalignant l esions before they become invasive and metastatic. One approach to controll ing preneoplastic lesions is to block their expansion with non-toxic agents that suppress cells proliferation and induce apoptosis. Here, we show that ellagic acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for 48 hours to colon cancer cells (SW 480), induced down regulation of insulin like growth factor IGF-II, activated P21((waf1/Cip1)), mediated a c umulative effect on G1/S transition phase and caused apoptotic cell death. SW480 colon cancer cells expressed significant mRNA levels for the mitogeni c insulin like growth factor (IGF-II). Collectively, these observations sug gest that growth inhibition by ellagic acid is mediated by signaling pathwa ys that mediate DNA damage, triggers p53, which in turn activates p21 and a t the same time alters the growth factor expression, resulting in the down regulation of IGF-II.