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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-5
pubmed:abstractText
Recent studies indicate that p53-dependent apoptosis induced in normal tissues during chemo- and radiotherapy can cause severe side effects of anti-cancer treatments that limit their efficiency. The aim of the present work was to further characterise the role of p53 in maintaining genomic stability and to verify whether the inhibition of p53 function in normal cells by pifithrin-alpha (PFT-alpha) may contribute in reducing the side effects of cancer therapy. Two human lymphoblastoid cell lines, derived from the same donor, TK6 (p53 wild type) and WTK1 (p53 mutated) have been treated with an anti-neoplastic drug, the etoposide (VP16), an inhibitor of DNA topoisomerase II in presence or in absence of the p53 inhibitor PFT-alpha. Following treatments with VP16 on TK6 and WTK1, we observed a higher induction of chromosome aberrations in WTK1 (p53 mutated) and of apoptosis in TK6 (p53 wild-type) cells. The p53 inhibition by PFT-alpha in VP16 treated TK6 cells produced an increase of chromosomal aberrations and a reduction of apoptosis. Therefore, the temporary suppression of the function of p53 by PFT-alpha, increasing the survival of the normal cells, could be a promising approach to reduce the side-effects of cancer therapy but it is important to consider that the surviving cells could be genetically modified and consequently the risk of secondary tumours could be increased.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
499
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
163-76
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:11827710-Antineoplastic Agents, Phytogenic, pubmed-meshheading:11827710-Benzothiazoles, pubmed-meshheading:11827710-Cell Cycle, pubmed-meshheading:11827710-Cell Survival, pubmed-meshheading:11827710-Chromosome Aberrations, pubmed-meshheading:11827710-DNA Fragmentation, pubmed-meshheading:11827710-Dose-Response Relationship, Drug, pubmed-meshheading:11827710-Drug Synergism, pubmed-meshheading:11827710-Etoposide, pubmed-meshheading:11827710-Flow Cytometry, pubmed-meshheading:11827710-Humans, pubmed-meshheading:11827710-Karyotyping, pubmed-meshheading:11827710-Lymphocytes, pubmed-meshheading:11827710-Thiazoles, pubmed-meshheading:11827710-Time Factors, pubmed-meshheading:11827710-Toluene, pubmed-meshheading:11827710-Tumor Cells, Cultured, pubmed-meshheading:11827710-Tumor Suppressor Protein p53
pubmed:year
2002
pubmed:articleTitle
Pifithrin-alpha, an inhibitor of p53, enhances the genetic instability induced by etoposide (VP16) in human lymphoblastoid cells treated in vitro.
pubmed:affiliation
Dipartimento di Agrobiologia e Agrochimica, Universita' degli Studi della Tuscia, Via San Camillo De Lellis, 01100, Viterbo, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't