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

Title
Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism
Authors
Jun Hee LimSeon Min WooKyoung-jin MinEun Jung ParkJi Hoon JangBo Ram SeoTaha IqbalTae-Jin LeeSang Hyun KimYung Hyun ChoiTaeg Kyu Kwon
Keimyung Author(s)
권택규
Department
Dept. of Immunology (면역학)
Issue Date
2012
Publisher
School of Medicine
Citation
Chemico-Biological Interactions, Vol.197(1) : 1-7, 2012
Abstract
Rottlerin, a selective inhibitor of novel isoforms of protein kinase C δ (PKC δ), 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- 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 δ, PKC δ siRNA and overexpression of dominant-negative (DN)-PKC δ did not affect rottlerin-mediated induction of NAG-1. These results suggest that rottlerin induces NAG-1 upregulation via a PKC δ-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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/17054
ISSN
0009-2797
Appears in Collections:
1. 연구논문 > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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