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Dicoumarol sensitizes renal cell carcinoma Caki cells toTRAIL-induced apoptosis through down-regulation of Bcl-2, Mcl-1 and c-FLIP in a NQO1-independent manner

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Author(s)
Eun Jung ParkKyoung-jin MinKyeong Sook ChoiTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Experimental Cell Research
Issued Date
2014
Volume
323
Issue
1
Abstract
In thestudy,weinvestigatedtheeffectofdicoumarol,ananti-coagulantagentwiththeinhibitory
activity ofNAD(P)Hquinoneoxidoreductase1(NQO1),onTRAIL-inducedapoptosisinrenal
cancer cell.CombinedtreatmentwithdicoumarolandTRAILsignificantly inducedapoptosisin
varioushumanrenalcarcinomacellsincludingCaki,ACHN,andA498,butnotinnormalhuman
skin fibroblasts (HSF)andmousekidneycells(TMCK-1).Whenweelucidatedtherelevanceof
NQO1 indicoumarolplusTRAIL-mediatedapoptosis,bothES936(aNQO1inhibitor)and
knockdownofNQO1withsiRNAhadnoeffectonTRAIL-mediatedapoptosis,suggestingthat
the stimulatingeffectofdicoumarolonTRAIL-mediatedapoptosisisindependentofNQO1
activity.Wefoundthatdicoumaroltranscriptionallydown-regulatedBcl-2expressionvia
inhibition ofNF-κB andCREBactivity,whereasitdown-regulatedMcl-1andc-FLIPexpression
at thepost-translationallevel.OverexpressionofBcl-2,Mcl-1,orc-FLIPovercamethedicoumarol
plus TRAIL-inducedapoptosis,indicatingthatdown-regualtionoftheseanti-apoptoticproteins
may criticallycontributetothesensitizingeffectofdicoumarolonTRAIL-mediatedapoptosis.
https://ac.els-cdn.com/S1067251614001392/1-s2.0-S1067251614001392-main.pdf?_tid=8d4712b8-2b0e-46c1-a0f7-7657c3d12d06&acdnat=1525932573_7c403df260b6eb00a9ef10e9914a8b1d
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Eun Jung Park et al. (2014). Dicoumarol sensitizes renal cell carcinoma
Caki cells toTRAIL-induced apoptosis through
down-regulation of Bcl-2, Mcl-1 and c-FLIP in a
NQO1-independent manner. Experimental Cell Research, 323(1), 144–154. doi: 10.1016/j.yexcr.2014.01.009
Type
Article
ISSN
0014-4827
Source
https://www.sciencedirect.com/science/article/pii/S0014482714000172?via%3Dihub
DOI
10.1016/j.yexcr.2014.01.009
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35729
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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