Linked Life Data

12481413

Source:http://linkedlifedata.com/resource/pubmed/id/12481413

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-12-16
pubmed:abstractText
We developed an original in vitro model dedicated to the exploration of molecular pharmacology of the new oral fluoropyrimidine capecitabine (Xeloda). More specifically, in this report, we investigated whether apoptosis induced by capecitabine was mediated by the Fas/FasL system. To achieve this goal, a specific in vitro coculture model mixing hepatoma and human colorectal cell line was used. A bystander effect was observed between HepG2 and LS174T cells treated with capecitabine. Besides this, Xeloda showed a 7-fold higher cytotoxicity and markedly stronger apoptotic potential in thymidine phosphorylase (TP)-transfected LS174T-c2 cells. The striking enhancement of thymidylate synthase inhibition that we observed in cells with high TP activity was most probably at the origin of the potentiation of capecitabine antiproliferative efficacy. In addition, this increase of sensitivity was accompanied by a strong overexpression of the CD95-Fas receptor on the cell surface. Both Fas and FasL mRNA expression were triggered after exposing TP+ cells to the drug. This implication of Fas in Xeloda-induced apoptosis was next confirmed by using antagonistic anti-Fas and anti-FasL antibodies that proved to reverse capecitabine antiproliferative activity, thus highlighting the key role that Fas could play in the optimization of an antitumor response to fluoropyrimidine drugs. Our data, therefore, show that TP plays a key role in the capecitabine activity and that the Fas/FasL system could be considered as a new determinant for Xeloda efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
923-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12481413-Antigens, CD95, pubmed-meshheading:12481413-Antimetabolites, Antineoplastic, pubmed-meshheading:12481413-Apoptosis, pubmed-meshheading:12481413-Bystander Effect, pubmed-meshheading:12481413-Cell Division, pubmed-meshheading:12481413-Cell Membrane, pubmed-meshheading:12481413-Colorectal Neoplasms, pubmed-meshheading:12481413-Deoxycytidine, pubmed-meshheading:12481413-Dose-Response Relationship, Drug, pubmed-meshheading:12481413-Fas Ligand Protein, pubmed-meshheading:12481413-Fluorouracil, pubmed-meshheading:12481413-Humans, pubmed-meshheading:12481413-Membrane Glycoproteins, pubmed-meshheading:12481413-RNA, Messenger, pubmed-meshheading:12481413-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12481413-Thymidylate Synthase, pubmed-meshheading:12481413-Time Factors, pubmed-meshheading:12481413-Transfection, pubmed-meshheading:12481413-Tumor Cells, Cultured
pubmed:year
2002
pubmed:articleTitle
Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas.
pubmed:affiliation
Laboratoire de Toxicocinétique et Pharmacocinétique, Faculté de Pharmacie, 27, Boulevard Jean Moulin, 13385 Marseille, France. joseph.ciccolini@pharmacie.univ-mrs.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't