Linked Life Data

20932751

Source:http://linkedlifedata.com/resource/pubmed/id/20932751

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2010-10-19
pubmed:abstractText
In the present study, we investigated the effect of a novel 3-arylisoquinoline derivative 3-(6-ethyl-benzo[1,3]dioxol-5-yl)-7,8-dimethoxy-2-methyl-2H-isoquinolin-1-one (CWJ-081) on the induction of apoptosis and the putative molecular mechanism of its action in human leukemia cells. Treatment with CWJ-081 exhibited a characteristic feature of apoptosis including externalization of phosphatidylserine and formation of DNA fragmentation in human leukemia cell lines (HL-60, U-937, K-562). In addition, stimulation of HL-60 cells with CWJ-081 induced a series of intracellular events: (1) the activations of caspase-8, -9, and -3; (2) the cleavage of poly (ADP-ribose) polymerase-1 (PARP-1); (3) the loss of mitochondrial membrane potential (??(m)); (4) the release of cytochrome c; and (5) the modulation of Bcl-2 family proteins. We further demonstrated that CWJ-081 induces reactive oxygen species (ROS) production and c-Jun NH(2)-terminal kinase (JNK) activation. Pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) markedly inhibited the CWJ-081-induced JNK activation and apoptosis. Moreover, CWJ-081-induced apoptosis was suppressed in the presence of SP600125, a specific JNK inhibitor. Taken together, these data suggest that CWJ-081 induces apoptosis via the mitochondrial apoptotic pathway in HL-60 cells, and ROS-mediated JNK activation plays a key role in the CWJ-081-induced apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1464-3405
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6447-51
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
CWJ-081, a novel 3-arylisoquinoline derivative, induces apoptosis in human leukemia HL-60 cells partially involves reactive oxygen species through c-Jun NH2-terminal kinase pathway.
pubmed:affiliation
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't