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Melatonin-mediated Bim up-regulation and cyclooxygenase-2 (COX-2) down-regulation enhances tunicamycin-induced apoptosis in MDA-MB-231 cells

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Author(s)
Seon Min WooKyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Journal of Pineal Research
Issued Date
2015
Volume
58
Issue
3
Keyword
apoptosisCOX-2melatoninNF-jBp38 MAPKtunicamycin
Abstract
Melatonin is involved in many physiological functions, and it has differential effects on apoptosis in normal and cancer cells. However, the mechanism of its antitumor roles is not well understood. In this study, we show that melatonin enhances tunicamycin-induced apoptosis in human breast carcinoma MDA-MB-231 cells. Melatonin up-regulates pro-apoptotic protein Bim expression at the transcriptional levels in the presence of tunicamycin. Melatonin inhibits tunicamycin-induced COX-2 expression in MDA-MB-231 cells. Furthermore, inhibition of COX-2 activity using the COX-2 inhibitor, NS398, increases tunicamycin-induced apoptosis. Interestingly, these effects were not associated with melatonin receptor signal pathways. Pertussis toxin (a general Gi protein inhibitor) or luzindole (a nonspecific melatonin receptor antagonist) did not reverse the effect of melatonin. In addition, melatonin blocked tunicamycin-induced NF-κB transcriptional activity, p65 nuclear translocation, and p38 MAPK activation. Melatonin-mediated p38 MAPK inhibition contributed to decreased COX-2 mRNA stability. Taken together, our results suggest that melatonin enhances antitumor function through up-regulation of Bim expression and down-regulation of COX-2 expression in tunicamycin-treated MDA-MB-231 cells.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Seon Min Woo et al. (2015). Melatonin-mediated Bim up-regulation and cyclooxygenase-2
(COX-2) down-regulation enhances tunicamycin-induced
apoptosis in MDA-MB-231 cells. Journal of Pineal Research, 58(3), 310–320. doi: 10.1111/jpi.12217
Type
Article
ISSN
0742-3098
Source
http://lps3.onlinelibrary.wiley.com.proxy.dsmc.or.kr/doi/abs/10.1111/jpi.12217
DOI
10.1111/jpi.12217
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34238
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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