Linked Life Data

16904205

Source:http://linkedlifedata.com/resource/pubmed/id/16904205

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-9-12
pubmed:abstractText
We present evidence that pyrrolidine dithiocarbamate (PDTC) inhibits growth of p53-negative pancreatic adenocarcinoma cell lines via cell cycle arrest in the S-phase, while it has no effect on primary fibroblast proliferation. Growth inhibition of cancer cells is dependent on ROS and ERK1/2 induction as indicated by a significantly reduced PDTC-associated growth inhibition by the free radical scavenger N-acetyl-L-cysteine (NAC) or the MEK/ERK1/2 inhibitor (PD98059). Moreover, ERK1/2 induction is dependent on ROS production as demonstrated by a complete removal of PDTC-mediated ERK1/2 phosphorylation by NAC. p21(WAF1/CIP1) activation has a central role in growth inhibition by PDTC, as revealed by P21(WAF1/CIP1) silencing experiments with antisense oligonucleotide, and occurs via increased mRNA stability largely mediated by ROS/ERK induction. Conversely, PDTC does not affect P21(WAF1/CIP1) gene expression in primary fibroblasts, although it is able to activate p53 and the p53-regulated antioxidant SESN2. These results suggest that the resistance of fibroblasts to the cytotoxic action of PDTC may be related to the up-regulation of p53-dependent antioxidant genes. Finally, in vivo studies on PaCa44 cells subcutaneously xenografted in nude mice show that treatment with 100 or 200 mg/kg PDTC reduces of 30% or 60% the tumour volume, respectively, and does not cause any apparent form of toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1763
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
917-26
pubmed:meshHeading
pubmed-meshheading:16904205-Acetylcysteine, pubmed-meshheading:16904205-Adenocarcinoma, pubmed-meshheading:16904205-Animals, pubmed-meshheading:16904205-Cell Cycle, pubmed-meshheading:16904205-Cell Line, Tumor, pubmed-meshheading:16904205-Cell Proliferation, pubmed-meshheading:16904205-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:16904205-DNA Primers, pubmed-meshheading:16904205-Fibroblasts, pubmed-meshheading:16904205-Flavonoids, pubmed-meshheading:16904205-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16904205-Gene Silencing, pubmed-meshheading:16904205-Humans, pubmed-meshheading:16904205-Immunoblotting, pubmed-meshheading:16904205-Mice, pubmed-meshheading:16904205-Oligonucleotides, Antisense, pubmed-meshheading:16904205-Pancreatic Neoplasms, pubmed-meshheading:16904205-Pyrrolidines, pubmed-meshheading:16904205-RNA Stability, pubmed-meshheading:16904205-Reactive Oxygen Species, pubmed-meshheading:16904205-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16904205-Thiocarbamates
pubmed:year
2006
pubmed:articleTitle
Increased stability of P21(WAF1/CIP1) mRNA is required for ROS/ERK-dependent pancreatic adenocarcinoma cell growth inhibition by pyrrolidine dithiocarbamate.
pubmed:affiliation
Department of Morphological and Biomedical Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't