Abstract 567: Inhibition of growth and induction of differentiation by apigenin, baicalein and quercetin in colon cancer cells

Abstract

Abstract There is considerable data to support the concept that polyphenolic molecules that occur in fruits and vegetables may have beneficial effects as cancer chemopreventive agents. We have shown previously that these polyphenolic molecules can induce enzyme markers of differentiation either alone, or in combination with histone deacetylase (HDAC) inhibitors. These data raise the question whether the induction of enzyme markers for differentiation are due to the anti- or pro-oxidant properties of polyphenols. We have compared the action of three flavonol molecules, apigenin, baicalein, and quercetin on four cell lines derived from human colon cells (Caco-2, SW1116, HT-29, and NCM460). The three polyphenols caused increases in alkaline phosphatase activity but no increase or decrease in aminopeptidase activity in Caco-2 cells. There was no induction of differentiation in the other cell lines by the three polyphenols. Since production of hydrogen peroxide has been reported when some polyphenolic compounds are incubated with serum-containing medium, we examined this phenomenon with the three polyphenols. Production of hydrogen peroxide was greater with baicalein than with quercetin or apigenin. When Caco-2 cells were incubated with hydrogen peroxide, there was some increase in alkaline phosphatase, but the concentrations required were higher than for the polyphenols and the magnitude of the effect was less. Further studies were performed with baicalein because that molecule had resulted in greater production of hydrogen peroxide. To test the significance of the hydrogen peroxide formation, we added catalase, but this addition did not prevent the increase in alkaline phosphatase or the decrease in protein synthesis in Caco-2 cells after incubation with baicalein. In addition, we wanted to determine the potential of the three polyphenols in combination with butyrate to increase the activity of alkaline phosphatase in Caco-2 cells. Synergistic effects were seen for the increase in alkaline phosphatase activity in Caco-2 cells for baicalein and quercetin, but not with apigenin. In conclusion, Caco-2 human colon cancer cells are notably sensitive to growth inhibitory and differentiating effects of apigenin, baicalein, and quercetin. It was evident that these polyphenols can have pro-oxidant effects, but our data suggested that this action was not the sole determinant of growth inhibitory or differentiating effects on colon cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 567.