Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC delta-independent mechanism

Title
Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC delta-independent mechanism
Author(s)
이태진권택규[권택규]임준희[임준희]우선민[우선민]민경진[민경진]박은정[박은정]장지훈[장지훈]서보람[서보람]Taha Iqbal[Taha Iqbal]김상현[김상현]최영현[최영현]
Keywords
TGF-BETA SUPERFAMILY; ACTIVATED GENE NAG-1; CANCER CELLS; TRANSGENIC MICE; EXPRESSION; PROTEIN; MEMBER; CYCLOOXYGENASE; INHIBITION; IDENTIFICATION
Issue Date
201204
Publisher
ELSEVIER IRELAND LTD
Citation
CHEMICO-BIOLOGICAL INTERACTIONS, v.197, no.1, pp.1 - 7
Abstract
Rottlerin, a selective inhibitor of novel isoforms of protein kinase C delta (PKC delta), has been shown to exert multiple effects on cancer cells, including inhibition of cell proliferation and migration. However, the molecular mechanisms responsible for these effects are not fully understood. We found that rottlerin dramatically induced non-steroidal anti-inflammatory drug activated gene-1 (NAG-1) expression in both p53 wild-type and p53-null cancer cell lines, suggesting that NAG-1 upregulation is a common response to rottlerin that occurs independently of p53 in multiple cell lines. Although rottlerin is known to inhibit PKC delta, PKC delta siRNA and overexpression of dominant-negative (DN)-PKC delta did not affect rottlerin-mediated induction of NAG-1. These results suggest that rottlerin induces NAG-1 upregulation via a PKC delta-independent pathway. We also observed that CHOP protein levels were significantly increased by rottlerin, but CHOP siRNA did not affect rottlerin-induced NAG-1 expression. In addition, we demonstrated the involvement of the mitogen-activated protein kinase (MAP kinase) signal transduction pathway in rottlerin-induced NAG-1 expression. Inhibitors of MEK (PD98059) and p38 MAP kinase (SB203580) prevented rottlerin-induced NAG-1 expression. Furthermore, we found that down-regulation of NAG-1 attenuated rottlerin-induced apoptosis. Collectively, the results of this study demonstrate, for the first time, that upregulation of NAG-1 contributes to rottlerin-induced apoptosis in cancer cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28627http://dx.doi.org/10.1016/j.cbi.2012.02.003
ISSN
0009-2797
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의과대학 > 해부학교실 > Articles
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