Linked Life Data

7796405

Source:http://linkedlifedata.com/resource/pubmed/id/7796405

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
1995-8-1
pubmed:abstractText
[(3,5-Di-tert-butyl-4-hydroxybenzylidene)-malononitrile] (AG17), a "tyrphostin" tyrosine kinase antagonist, was found to inhibit tumor cell growth with 50% growth inhibition ranging from 0.7 to 4.0 microM in a panel of 13 human tumor cell lines, as evaluated by tetrazolium dye reduction and inhibition of precursor incorporation into macromolecules. The promyelocytic leukemia cell line HL-60(TB), was the most sensitive with irreversible total growth inhibition after 12 h of exposure to 1.5 microM drug. Antiproliferative effects of AG17 in HL-60(TB) cells were temporally related to disruption of mitochondrial function, which occurred within 1 h after drug exposure as demonstrated by a significantly decreased mass of ATP in drug-treated cells, loss of the fluorescent mitochondrial membrane potential probe rhodamine 123, and ultrastructural examination of mitochondria using fluorescence and electron microscopy. Specific decreases of total or tyrosine-phosphorylated substrate at concentrations of the drug not affecting ATP levels were not detected. These data raise the possibility that AG17 may act in part by altering mitochondrial function and/or structure, and that impairment of mitochondrial function may be exploitable as a potentially useful mechanism to modulate tumor cell proliferation. This study also emphasizes the importance of evaluating carefully the effects of potential protein kinase antagonists, since these structures have effects in intact cells in addition to what might be expected from in vitro enzyme assays.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2794-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Tyrphostin AG17, [(3,5-Di-tert-butyl-4-hydroxybenzylidene)- malononitrile], inhibits cell growth by disrupting mitochondria.
pubmed:affiliation
PRI/DymCorp, Frederick Cancer Research and Development Center, Maryland 21701, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't