[Deguelin regulates cell cycle and nuclear pore complex protein Nup98 and Nup88 in U937 cells in vitro].
OBJECTIVE
To investigate antitumor activity and molecular mechanism of deguelin to the human U937 leukaemia cells and to explore the mechanisms regulating cell cycle and 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, and the cell cycle of U937 cells by a propidium iodide method. The localization of the nuclear pore complex protein Nup98 and Nup88 was checked by immunofluorescence and immunoelectron microscopy. The expressions of Nup98 and Nup88 in U937 cells were checked by flow cytometry (FCM) and Western blot respectively.


RESULTS
The proliferation of U937 cells was significantly inhibited in a time-dose dependent manner in deguelin-treated group with a 24 h IC50 value of 21.61 nmol/L and 36 h IC50 value of 17.07 nmol/L. U937 cells treated with deguelin showed reduction in the percentages of cells in G0/G1, whereas accumulation of cells in S and G2/M phase. The ratio of G1/G0 phase cells were 73.01%, 71.15%, 68.42%, 52.45%, 43.99% and 22.82%, and that of S phase cells were 17.18%, 16.30%, 18.09%, 27.56%, 31.21% and 46.85%, and that of G2/M phase cells were 9.75%, 12.31%, 13.09%, 18.99%, 24.83% and 27.79% at deguelin concentrations of 0, 5, 10, 20, 40, 80 nmol/L respectively. Nup88 and Nup98 were found on both the nuclear and cytoplasmic side of the U937 cells. The expression of Nup98 was up-regulated and Nup88 down-regulated in deguelin treated U937 cells.


CONCLUSIONS
Deguelin is able to inhibit the proliferation of U937 cells by regulating the cell cycle. The antitumor activity of deguelin was related to up-regulating the expression of Nup98 and down-regulating Nup88 protein.
Chen
Yan
Y
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Liu
Hong-Li
HL
Cui
Guo-Hui
GH
Wu
Qiu-Ling
QL
He
Jing
J
Chen
Wei-Hua
WH
D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology; D020298:U937 Cells
C104835:NUP88 protein, human; D028861:Nuclear Pore Complex Proteins; C465451:Nup98 protein, human; D012402:Rotenone; C107676:deguelin