Linked Life Data

16077967

Source:http://linkedlifedata.com/resource/pubmed/id/16077967

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-8-3
pubmed:abstractText
Protein phosphatases have been classified into two basic types, namely protein serine/threonine phosphatase (PP), and protein tyrosine phosphatase (PTP). Cpd 5 is a selective inhibitor of cdc25 phosphatases, which belong to members of PTPs and regulate cell proliferation by controlling cyclin-dependent kinases (cdks). The present study was undertaken to investigate the potential utility of Cpd 5 as an anti-neoplastic agent for renal cell carcinomas (RCCs). Three renal cancer cell lines, 769P, Sw839, and A498 were used. The effects of Cpd 5 on the viability of renal cancer cell lines was analyzed using an Alamar Blue assay. Apoptosis was determined by flow cytometric TUNEL analysis. Changes in the expression of cdc25 phosphatases, mitogen-activated protein kinases (MAPKs), and bcl-2 family proteins were detected using Western blot analysis. The apoptosis-inducing effect of Cpd 5 on human RCC tissue was analyzed through TUNEL staining of organ cultures from RCCs. Cpd 5 showed a strong cytotoxicity against all renal cancer cell lines with an apoptosis-inducing effect. All cell lines treated with Cpd 5 resulted in a down-regulation of cdc25A, cdc25B, and cdc25C, however, the MAPK pathways were not affected. In addition, the up-regulation of bax, and the down-regulation of bcl-2 and bcl-xL, was observed. In organ cultures from RCCs, TUNEL-positive apoptotic nuclei were observed when treated with Cpd 5. Cpd 5 was thus found to effectively inhibit the proliferation of human renal cancer cells while also inducing apoptosis by inhibiting cdc25 phosphatases and modulating bcl-2 family proteins. The administration of Cpd 5 may thus be an effective therapeutic approach for RCCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
639-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Modulation of bcl-2 family proteins in MAPK independent apoptosis induced by a cdc25 phosphatase inhibitor Cpd 5 in renal cancer cells.
pubmed:affiliation
Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't