Colorectal cancer is one of the most common cancers in the world, poorly responding to available chemotherapeutic agents. To investigate whether natural molecules can inhibit colon cancer progression, we investigated a principle phytoestrogen found in soybean known as daidzein, and determined its effects on the human colon cancer cell line LoVo. LoVo cells were treated with 0.1, 1, 5, 10, 50 and 100 muM daidzein for 2, 3, 4 or 5 d. The results indicated that daidzein stimulated the growth of LoVo cells at 0.1 and 1 muM whereas at higher concentrations (10, 50 and 100 muM) cell growth was inhibited in a dose-dependent manner. Treatment of daidzein at 10, 50 and 100 muM resulted in cell cycle arrest at G0/G1 phase, DNA fragmentation and increases in caspase-3 activity. There were no changes in alkaline phosphatase activity (ALP), an indicator of cell differentiation, upon treatment with daidzein when compared to controls. These results indicate that daidzein has a biphasic effect on LoVo cell growth and its tumor suppressive effect is by means of cell cycle arrest and apoptosis but not through cell differentiation. (C) 2004 Elsevier Ltd. All rights reserved.