Linked Life Data

19459175

Source:http://linkedlifedata.com/resource/pubmed/id/19459175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-11-2
pubmed:abstractText
Growth suppressive effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic, against cultured human cancer cells correlates with checkpoint kinase 1 (Chk1)-mediated mitotic arrest, but the fate of the cells arrested in mitosis remains elusive. Using LNCaP and HCT-116 human cancer cells as a model, we now demonstrate that the Chk1-mediated mitotic arrest resulting from DATS exposure leads to apoptosis. The DATS exposure resulted in G(2) phase and mitotic arrest in both LNCaP and HCT-116 cell lines. The G(2) arrest was accompanied by downregulation of cyclin-dependent kinase 1 (Cdk1), cell division cycle (Cdc) 25B, and Cdc25C leading to Tyr15 phosphorylation of Cdk1 (inactivation). The DATS-mediated mitotic arrest correlated with inactivation of anaphase-promoting complex/cyclosome as evidenced by accumulation of its substrates cyclinB1 and securin. The DATS treatment increased activating phosphorylation of Chk1 (Ser317) and transient transfection with Chk1-targeted siRNA conferred significant protection against DATS-induced mitotic arrest in both cell lines. The Chk1 protein knockdown also afforded partial yet statistically significant protection against apoptotic DNA fragmentation and caspase-3 activation resulting from DATS exposure in both LNCaP and HCT-116 cells. Even though DATS treatment resulted in stabilization and Ser15 phosphorylation of p53, the knockdown of p53 protein failed to rescue DATS-induced mitotic arrest. In conclusion, the results of the present study indicate that Chk1 dependence of DATS-induced mitotic arrest in human cancer cells is not influenced by the p53 status and cells arrested in mitosis upon DATS exposure are driven to apoptotic DNA fragmentation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1098-2744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1018-29
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Diallyl trisulfide-induced apoptosis in human cancer cells is linked to checkpoint kinase 1-mediated mitotic arrest.
pubmed:affiliation
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural