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

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Author(s)
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)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Chemico-Biological Interactions
Issued Date
2012
Volume
197
Issue
1
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-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 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.
Keywords
Rottlerin;
NAG-1;
Apoptosis;
p53;
Colon carcinoma cells
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Jun Hee Lim et al. (2012). Rottlerin induces apoptosis of HT29 colon carcinoma cells through NAG-1 upregulation via an ERK and p38 MAPK-dependent and PKC δ-independent mechanism. Chemico-Biological Interactions, 197(1), 1–7. doi: 10.1016/j.cbi.2012.02.003
Type
Article
ISSN
0009-2797
Source
https://www.sciencedirect.com/science/article/pii/S0009279712000300?via%3Dihub
DOI
10.1016/j.cbi.2012.02.003
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35393
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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