Linked Life Data

15634646

Source:http://linkedlifedata.com/resource/pubmed/id/15634646

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-1-6
pubmed:abstractText
DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)-containing complexes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1533-42
pubmed:dateRevised
2008-6-2
pubmed:meshHeading
pubmed-meshheading:15634646-Animals, pubmed-meshheading:15634646-Antineoplastic Agents, pubmed-meshheading:15634646-Apoptosis, pubmed-meshheading:15634646-Chlorine Compounds, pubmed-meshheading:15634646-DNA-Binding Proteins, pubmed-meshheading:15634646-Enzyme Activation, pubmed-meshheading:15634646-Female, pubmed-meshheading:15634646-Humans, pubmed-meshheading:15634646-Mice, pubmed-meshheading:15634646-Mice, Inbred BALB C, pubmed-meshheading:15634646-NIH 3T3 Cells, pubmed-meshheading:15634646-Neoplasms, Experimental, pubmed-meshheading:15634646-Organoplatinum Compounds, pubmed-meshheading:15634646-Phosphorylation, pubmed-meshheading:15634646-Platinum Compounds, pubmed-meshheading:15634646-STAT3 Transcription Factor, pubmed-meshheading:15634646-Signal Transduction, pubmed-meshheading:15634646-Trans-Activators, pubmed-meshheading:15634646-Tumor Cells, Cultured, pubmed-meshheading:15634646-Xenograft Model Antitumor Assays
pubmed:year
2004
pubmed:articleTitle
Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity.
pubmed:affiliation
Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. turksonj@moffitt.usf.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.