Linked Life Data

16287083

Source:http://linkedlifedata.com/resource/pubmed/id/16287083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-2-21
pubmed:abstractText
The marine plitidepsin Aplidin derived from the Mediterranean tunicate Aplidium albicans is a strong apoptotic inducer with promising antitumor activity. However, little is known about the mechanism of action of the molecule. In this article, we report that Aplidin is cytotoxic for NIH3T3 cells and that its action is exerted through the production of reactive oxygen species (ROS). Rotenone, but not other selective inhibitors of ROS production, blocks the induction of ROS, suggesting the involvement of the mitochondrial respiratory chain in Aplidin action. The intracellular rise of redox potential caused by Aplidin inactivates several molecular targets. Among these targets, we focused our attention on protein tyrosine phosphatases (PTPs). In agreement with the well-characterized effect of ROS-mediated PTP oxidation, due to the presence of a cysteine residue in their catalytic site, we found that Aplidin induces a strong decrease in PTP activity. In particular, since the expression of low molecular weight-PTP (LMW-PTP) is strongly associated with tumor onset and progression, we investigated the effect of Aplidin on this enzyme. Our data show that LMW-PTP is oxidized and inactivated during Aplidin treatment, thus causing a hyper-phosphorylation of its substrate beta-catenin. These findings demonstrate that, at least in part, the antitumoral activity of Aplidin could be due to the direct inhibition of LMW-PTP and its related oncogenic potential.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2082-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Oxidation and inactivation of low molecular weight protein tyrosine phosphatase by the anticancer drug Aplidin.
pubmed:affiliation
Department of Biochemical Sciences, University of Florence, viale Morgagni 50, 50134 Florence, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't