계명대학교 의학도서관 Repository

Induction of apoptosis by esculetin in human leukemia U937 cells: Roles of Bcl-2 and extracellular-regulated kinase signaling

Metadata Downloads
Author(s)
Cheol ParkCheng-Yun JinHyun Ju KwonHye Jin HwangGi-Young KimIl Whan ChoiTaeg Kyu KwonByung-Woo KimWun-Jae KimYung Hyun Choi
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Toxicol In Vitro
Issued Date
2010
Volume
24
Issue
2
Keyword
EsculetinlApoptosisBcl-2HA14-1ERK
Abstract
In the present study, we reported that apoptosis induced by esculetin, a phenolic compound with apop-
totic activity in cancer cells, was markedly blocked by Bcl-2-overexpression, but restored by HA14-1, a
small-molecule Bcl-2 inhibitor, in human leukemic U937 cells. The combined use of esculetin and
HA14-1 effectively induced Bid cleavage and loss of mitochondrial membrane potential (MMP, Dwm)
leading to the activation of caspases and cleavage of poly(ADP-ribose) polymerase (PARP) in Bcl-2-over-
expressing (U937/Bcl-2) cells. Combined treatment with esculetin and HA14-1 upregulated the expres-
sion of death receptor 4 (DR4), and activation of extracellular-regulated kinase (ERK) in a time-
dependent manner. In addition, esculetin and HA14-1-mediated apoptosis was reduced by ERK inhibitors
through inhibition of DR4 expression, suggesting that the synergistic effect was at least partially medi-
ated through ERK-dependent induction of DR4 expression. The results indicate that HA14-1-induced
reversal of the anti-apoptotic effect of Bcl-2 confers apoptosis sensitivity to esculetin by a mitochondrial
amplification step and through the ERK-dependent induction of DR4 expression in U937/Bcl-2 cells. Thus,
HA14-1 reversal of Bcl-2-mediated esculetin resistance suggests a novel strategy for increasing esculetin
sensitivity in Bcl-2-overexpressing leukemia cells.
2009 Elsevier Ltd. All rights reserved. Keywords:
Esculetinl
Apoptosis
Bcl-2
HA14-1
ERK
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Cheol Park et al. (2010). Induction of apoptosis by esculetin in human leukemia U937 cells: Roles of Bcl-2 and extracellular-regulated kinase signaling. Toxicol In Vitro, 24(2), 486–494. doi: 10.1016/j.tiv.2009.09.017
Type
Article
ISSN
0887-2333
Source
http://lps3.www.sciencedirect.com.proxy.dsmc.or.kr/science/article/pii/S0887233309002847?via%3Dihub
DOI
10.1016/j.tiv.2009.09.017
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34668
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.