Linked Life Data

17513615

Source:http://linkedlifedata.com/resource/pubmed/id/17513615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-5-21
pubmed:abstractText
Previous studies have indicated that d,l-sulforaphane (SFN), a synthetic cancer chemopreventive analogue of cruciferous vegetable-derived isomer (-)-1-isothiocyanato-(4R)-(methylsulfinyl)-butane, activates a checkpoint kinase 2 (Chk2)-dependent G(2)-M phase cell cycle arrest in p53-deficient human prostate cancer cells. Because p53 is a downstream target of Chk2 kinase and known to regulate G(2)-M transition by transcriptional regulation of cyclin-dependent kinase (Cdk) inhibitor p21(Cip1/Waf1) (p21), the present study was undertaken to determine the role of p21 in SFN-induced cell cycle arrest using wild-type p53-expressing cell line LNCaP. The SFN treatment caused a modest increase in S phase fraction and a marked increase in G(2)-M fraction in LNCaP cells in a concentration- and time-dependent manner. The SFN-induced S phase arrest correlated with a reduction in protein levels of cyclin D1, cyclin E, Cdk4, and Cdk6, whereas activation of the G(2)-M checkpoint was accompanied by induction of cyclin B1 and down-regulation of Cdk1 and Cdc25C protein levels. The SFN-treated LNCaP cells were also arrested in mitosis as revealed by immunofluorescence microscopy and increased Ser(10) phosphorylation of histone H3, a sensitive marker for mitotic cells. The SFN treatment increased activating phosphorylation of Chk2 (Thr(68)) that was accompanied by induction of p53 and p21. The SFN-induced mitotic arrest was statistically significantly increased by small interfering RNA-based knockdown of p21. However, p21 protein knockdown did not have any appreciable effect on SFN-induced cytoplasmic histone-associated DNA fragmentation (apoptosis). In conclusion, the present study indicates that induction of p21 protects against SFN-induced mitotic arrest in LNCaP cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1673-81
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line.
pubmed:affiliation
Department of Molecular Biology, University of Gdask, Gdask, Poland.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural