Silibinin induces apoptosis of HT29 colon carcinoma cells through early CrossMark growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation

Title
Silibinin induces apoptosis of HT29 colon carcinoma cells through early CrossMark growth response-1 (EGR-1)-mediated non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) up-regulation
Author(s)
이태진우선민[우선민]민경진[민경진]김신[김신]박종욱[박종욱]김동은[김동은]전경수[전경수]김용호[김용호]김상현[김상현]최영현[최영현]권택규[권택규]장종수[장종수]
Keywords
TGF-BETA SUPERFAMILY; MACROPHAGE-INHIBITORY CYTOKINE; CANCER CELLS; TUMOR-GROWTH; EXPRESSION; MEMBER; PROTEIN; EGR-1; MICE; CYCLOOXYGENASE
Issue Date
201403
Publisher
ELSEVIER IRELAND LTD
Citation
CHEMICO-BIOLOGICAL INTERACTIONS, v.211, pp.36 - 43
Abstract
Silibinin, an effective anti-cancer and chemopreventive agent, has been shown to exert multiple effects on cancer cells, including inhibition of both cell proliferation and migration. However, the molecular mechanisms responsible for these effects are not fully understood. We observed that silibinin significantly induced the expression of the non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) in both p53 wild-type and p53-null cancer cell lines, suggesting that silibinin-induced NAG-I up-regulation is p53-independent manner. Silibinin up-regulates early growth response-1 (EGR-1) expression. The ectopic expression of EGR-1 significantly increased NAG-1 promoter activity and NAG-1 protein expression in a dose-dependent manner. Furthermore, down-regulation of EGR-1 expression using siRNA markedly reduced silibinin-mediated NAG-1 expression, suggesting that the expression of EGR-1 is critical for silibinin-induced NAG-1 expression. We also observed that reactive oxygen species (ROS) are generated by silibinin; however, ROS did not affect silibinin-induced NAG-1 expression and apoptosis. In addition, we demonstrated that the mitogen-activated protein kinase (MAP kinase) signal transduction pathway is involved in silibinin-induced NAG-I expression. Inhibitors of p38 MAP kinase (SB203580) attenuated silibinin-induced NAG-1 expression. Furthermore, we found that siRNA-mediated knockdown of NAG-I attenuated silibinin-induced apoptosis. Collectively, the results of this study demonstrate for the first time that up-regulation of NAG-1 contributes to silibinin-induced apoptosis in cancer cells. (c) 2014 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/32782http://dx.doi.org/10.1016/j.cbi.2014.01.004
ISSN
0009-2797
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의과대학 > 해부학교실 > Articles
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