Linked Life Data

19360349

Source:http://linkedlifedata.com/resource/pubmed/id/19360349

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-4-10
pubmed:abstractText
1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106) is a novel antitumor ribonucleoside that inhibits RNA polymerase. In the present study, we investigated the cellular and molecular interactions between TAS-106 and cisplatin (CDDP) in vitro using A549 human lung cancer cells and the in vivo antitumor effect of combined treatment using OCC-1 and LX-1 human tumor xenografts. The treatment effects were determined by evaluating cytotoxicity, the cell cycle distribution, apoptosis induction and the expression of checkpoint-associated proteins. In vitro, the combination of TAS-106 and CDDP synergistically inhibited the growth of A549 cells, as determined using isobologram analysis. TAS-106 potently inhibited the expression of Chk1 protein and the phosphorylation of Chk1 and Chk2. Moreover, based on the inhibition of checkpoint-associated protein, TAS-106 abrogated the CDDP-induced S- and G2M-checkpoints and induced apoptosis in A549 cells. In vivo, TAS-106 alone showed antitumor activity; however, its combination with CDDP significantly enhanced the growth inhibition of OCC-1 and LX-1 tumors. Moreover, combination therapy with TAS-106 and CDDP in the OCC-1 xenograft model resulted in significant life-prolongation. These findings provide a rationale for combination chemotherapy using TAS-106 and CDDP in clinical settings.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1373-80
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a novel potent inhibitor of RNA polymerase, potentiates the cytotoxicity of CDDP in human cancer cells both in vitro and in vivo.
pubmed:affiliation
Hanno Research Center, Taiho Pharmaceutical Co., Ltd., Hanno-city, Saitama 357-8527, Japan. h-kazuno@taiho.co.jp
pubmed:publicationType
Journal Article