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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0023418,
umls-concept:C0036536,
umls-concept:C0036537,
umls-concept:C0078058,
umls-concept:C0086418,
umls-concept:C0378516,
umls-concept:C0388638,
umls-concept:C0439659,
umls-concept:C0450442,
umls-concept:C0596138,
umls-concept:C1171892,
umls-concept:C1533157
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pubmed:issue |
1
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pubmed:dateCreated |
2003-1-16
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pubmed:abstractText |
The mechanism by which aplidine, a marine natural product in early clinical development as an anticancer agent, induces cell growth inhibition and apoptosis has been investigated in the human leukemia cell line MOLT-4. This cell line is characterized not only by the ability to secrete VEGF, but also for the presence on its surface of the VEGF receptor-1 (VEGFR-1). Previous studies from our laboratory concerned with evaluating early changes in gene expression induced by aplidine in MOLT-4 cells have shown that the drug decreases the expression of VEGFR-1 (Marchini et al. Proc Am Assoc Cancer Res 2000; 41: 833). Here, we report the ability of aplidine to block the VEGF/VEGFR-1 loop. We found that aplidine blocked VEGF secretion that was temporally followed by a decrease in both VEGF and VEGFR-1 production. Aplidine did not directly affect either VEGF transcription or stabilization of its mRNA. Transfection of MOLT-4 cells with an antisense VEGF cDNA construct, resulted in inhibition of colony formations. One clone, transfected with sense VEGF cDNA, secreting 8-10 times more VEGF than parental cells, was less sensitive to aplidine-induced cytotoxicity and apoptosis than control cells. Moreover, addition of VEGF in the medium decreased the activity of aplidine in MOLT-4 cells. These data demonstrate that aplidine inhibits the growth and induces apoptosis in MOLT-4 cells through the inhibition of VEGF secretion which blocks the VEGF/VEGFR-1 autocrine loop necessary for the growth of these cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Depsipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/aplidine
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0887-6924
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pubmed:author |
pubmed-author:BorsottiPP,
pubmed-author:BrogginiMM,
pubmed-author:D'IncalciMM,
pubmed-author:ErbaEE,
pubmed-author:FairclothG TGT,
pubmed-author:GallieraEE,
pubmed-author:GiavazziRR,
pubmed-author:JimenoJJ,
pubmed-author:MarchiniS VSV,
pubmed-author:SironiMM,
pubmed-author:TarabolettiGG
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
52-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12529660-Antineoplastic Agents,
pubmed-meshheading:12529660-Apoptosis,
pubmed-meshheading:12529660-Autocrine Communication,
pubmed-meshheading:12529660-Cell Division,
pubmed-meshheading:12529660-DNA Primers,
pubmed-meshheading:12529660-Dactinomycin,
pubmed-meshheading:12529660-Depsipeptides,
pubmed-meshheading:12529660-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:12529660-Endothelial Growth Factors,
pubmed-meshheading:12529660-Half-Life,
pubmed-meshheading:12529660-Humans,
pubmed-meshheading:12529660-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12529660-Leukemia, T-Cell,
pubmed-meshheading:12529660-Luciferases,
pubmed-meshheading:12529660-Lymphokines,
pubmed-meshheading:12529660-Peptides, Cyclic,
pubmed-meshheading:12529660-Polymerase Chain Reaction,
pubmed-meshheading:12529660-Promoter Regions, Genetic,
pubmed-meshheading:12529660-Protein Synthesis Inhibitors,
pubmed-meshheading:12529660-RNA, Messenger,
pubmed-meshheading:12529660-Signal Transduction,
pubmed-meshheading:12529660-Transfection,
pubmed-meshheading:12529660-Tumor Cells, Cultured,
pubmed-meshheading:12529660-Vascular Endothelial Growth Factor A,
pubmed-meshheading:12529660-Vascular Endothelial Growth Factor Receptor-1,
pubmed-meshheading:12529660-Vascular Endothelial Growth Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4.
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pubmed:affiliation |
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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