Piceatannol, a Natural Analog of Resveratrol, Inhibits Progression through the S Phase of the Cell Cycle in Colorectal Cancer Cell Lines

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Abstract
Piceatannol, a naturally occurring analog of resveratrol, was previously identified as the active ingredient in herbal preparations in folk medicine and as an inhibitor of p72Syk. We studied the effects of piceatannol on growth, proliferation, differentiation and cell cycle distribution profile of the human colon carcinoma cell line Caco-2. Growth of Caco-2 and HCT-116 cells was analyzed by crystal violet assay, which demonstrated dose- and time-dependent decreases in cell numbers. Treatment of Caco-2 cells with piceatannol reduced proliferation rate. No effect on differentiation was observed. Determination of cell cycle distribution by flow cytometry revealed an accumulation of cells in the S phase. Immunoblotting demonstrated that cyclin-dependent kinases (cdk) 2 and 6, as well as cdc2 were expressed at steady-state levels, whereas cyclin D1, cyclin B1 and cdk 4 were downregulated. The abundance of p27Kip1 was also reduced, whereas the protein level of cyclin E was enhanced. Cyclin A levels were enhanced only at concentrations up to 100 μmol/L. These changes also were observed in studies with HCT-116 cells. On the basis of our findings, piceatannol can be considered to be a promising chemopreventive or anticancer agent.