Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro1

Abstract

Aim: To investigate the anticancer effects and the molecular mechanisms of deguelin on human U937 leukemia cells, and to explore the underlying mechanism regulating nucleoporin 98 (Nup98) and nucleoporin 88 (Nup88) in vitro. Methods: The effects of deguelin on the growth of U937 cells were studied by MTT assay. The effect of deguelin on the cell cycle of U937 cells was studied by using a propidium iodide method. The localization of the nuclear pore complex proteins Nup98 and Nup88 was investigated by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 and Nup88 in U937 cells was investigated by using flow cytometry and Western blot. Results: The proliferation of U937 cells was inhibited in the deguelin-treated group, with a 24-h IC 50 value of 21.61 nmol/L and a 36-h IC 50 value of 17.07 nmol/L. U937 cells treated with deguelin had reduced percentages of cells in the G 0 /G 1 phase, whereas cells accumulated in the S and G 2 /M phases. Nup88 and Nup98 were found on both the nuclear and cytoplasmic sides of the U937 cells by using immunofluorescence and immunoelectron microscopy. The expression of Nup98 was upregulated and that of the Nup88 protein was downregulated in U937 cells treated with deguelin. Conclusion: Deguelin is able to inhibit the proliferation of U937 cells by regulating the cell cycle such that cells are arrested at the S and G 2 /M phases, so that the proportion of cells in the G 0 /G 1 phase decreases. The antitumor effects of deguelin are related to upregulating the expression of Nup98 and downregulating the expression of Nup88 protein in U937 cells. ©2005 CPS and SIMM.