title: Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liuhl60@tom.com
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Guo-hui
authors.initials: GH
authors.lastname: Cui
authors.forename: Qiu-ling
authors.initials: QL
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Chen
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae / Q000737:chemistry; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D010946:Plants, Medicinal / Q000737:chemistry; D012402:Rotenone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C104835:NUP88 protein, human; D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98; D012402:Rotenone; C107676:deguelin