Deguelin regulates nuclear pore complex proteins Nup98 and Nup88 in U937 cells in vitro.
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.
Liu
Hong-li
HL
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liuhl60@tom.com
Chen
Yan
Y
Cui
Guo-hui
GH
Wu
Qiu-ling
QL
He
Jing
J
Chen
Wei-hua
WH
Zhou
Jian-feng
JF
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
D000972:Antineoplastic Agents, Phytogenic; C104835:NUP88 protein, human; D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98; D012402:Rotenone; C107676:deguelin