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Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK

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Author(s)
Cheol ParkCheng-Yun JinGi-Young KimIl-Whan ChoiTaeg Kyu KwonByung Tae ChoiSu Jae LeeWon Ho LeeYung Hyun Choi
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Toxicology and Applied Pharmacology
Issued Date
2008
Volume
227
Issue
2
Keyword
EsculetinApoptosisBcl-2ERKJNK
Abstract
Esculetin is a phenolic compound that is found in various natural plant products and induces apoptosis in several types of human cancer cells.
However, the underlying mechanisms of its action are not completely understood. In the present study, we used human leukemia cells to gain further
insight into the mechanism of esculetin-induced anti-proliferative action and apoptosis. It was found that esculetin inhibits cell viability by inducing
apoptosis, as evidenced by the formation of apoptotic bodies, DNA fragmentation, and the accumulation of cells in the sub-G1 phase. Esculetin-induced
apoptosis was correlated with mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the
proteolytic activation of caspases. The z-DEVD-fmk caspase-3 inhibitor and the ectopic expression of anti-apoptotic Bcl-2 significantly inhibited
esculetin-induced apoptosis, demonstrating the important role of caspase-3 and mitochondrial proteins in the observed cytotoxic effect. Furthermore,
esculetin selectively increased the phosphorylation of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not that of other
kinases such asAkt and p38 activation. In addition, an ERK-specific inhibitor, PD98059, and a JNK-specific inhibitor, SP600125, showed inhibited sub-
G1 phase DNA content, DNA fragmentation, caspase activation, and mitochondrial dysfunction induced by esculetin treatment. These results indicated
that the JNK and ERK pathways were key regulators of apoptosis in response to esculetin in human leukemia U937 cells.
© 2007 Elsevier Inc. All rights reserved.
Keywords: Esculetin; Apoptosis; Bcl-2; ERK; JNK
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Cheol Park et al. (2008). Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK. Toxicology and Applied Pharmacology, 227(2), 219–228. doi: 10.1016/j.taap.2007.10.003
Type
Article
ISSN
0041-008X
Source
https://www.sciencedirect.com/science/article/pii/S0041008X07004462?via%3Dihub
DOI
10.1016/j.taap.2007.10.003
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34663
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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