Linked Life Data

12473386

Source:http://linkedlifedata.com/resource/pubmed/id/12473386

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-12-10
pubmed:abstractText
The present study was performed to gain insight into the role of p53 and p21(WAF1) on the cytotoxicity of the purine analogue cladribine (2-CdA) on cancer cells. Drug sensitivity, cell cycle distribution and drug-induced cell death were compared in three lines derived from the colorectal carcinoma HCT116: the p53+/+ cell line containing wild-type p53 and the p53-/- and p21(WAF1)-/- lines, in which both alleles of p53 or p21(WAF1) were deleted by homologous recombination, respectively. p53-/- and p21(WAF1)-/- cells were significantly more resistant to the cytotoxic effects of 2-CdA than the p53+/+ cells. p53+/+ cells and p21(WAF1)-/-, but not p53-/- cells, displayed wt-p53 protein accumulation and arrested in S-phase after exposure to 2-CdA. mRNA analysis of the transporter hENT1 and of enzymes involved in drug metabolism did not show alterations which might explain a drug-resistant phenotype in the p53-/- or p21(WAF1)-/- cells. Exposure of p53+/+ cells to 2-CdA resulted in expression of p21(WAF1) mRNA and protein, enhanced expression of uncleaved PARP-1, and a higher degree both of apoptosis and necrosis than in p53-/- and p21(WAF1)-/- cells exposed to 2-CdA. Addition of the specific PARP-1 inhibitor 3-AB to 2-CdA-treated cells rendered p53+/+ cells resistant to this drug. Bax levels were reduced in the p53-/- while they increased in the p53+/+ line and remained stable in the p21(WAF1)-/- cells. We conclude that p53 and p21(WAF1) status of cancer cells influences their sensitivity to 2-CdA cytotoxicity. This may involve alterations in the apoptotic cascade as well as in PARP-1-dependent cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Influence of p53 and p21(WAF1) expression on sensitivity of cancer cells to cladribine.
pubmed:affiliation
INSERM 453. 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France. fgalma@rockefeller.univ-lyon1.fr
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't