Linked Life Data

16965246

Source:http://linkedlifedata.com/resource/pubmed/id/16965246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-9-12
pubmed:abstractText
We have shown recently that diallyl trisulfide (DATS), a cancer-chemopreventive constituent of garlic, inactivates Akt to trigger mitochondrial translocation of proapoptotic protein BAD in human prostate cancer cells. Because Akt activation is implicated in the promotion of endothelial cell survival and angiogenesis, we hypothesized that DATS may inhibit angiogenesis. In the present study, we tested this hypothesis using human umbilical vein endothelial cells (HUVECs) as a model. Survival of HUVECs was reduced significantly in the presence of DATS in a concentration-dependent manner, with an IC50 of approximately 4 microM. The DATS-mediated suppression of HUVEC survival was associated with apoptosis induction characterized by accumulation of subdiploid cells, cytoplasmic histone-associated DNA fragmentation, and cleavage of caspase-3 and poly-(ADP-ribose)-polymerase. The DATS-induced DNA fragmentation was significantly attenuated in the presence of pan-caspase inhibitor zVAD-fmk and specific inhibitors of caspase-9 (zLEHD-fmk) and caspase-8 (zIETD-fmk). DATS treatment inhibited the formation of capillary-like tube structure and migration by HUVECs in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level and inactivation of Akt kinase. DATS treatment also caused activation of extracellular signal-regulated kinase 1/2 (ERK1/2) but not c-Jun NH2-terminal kinase (JNK) or p38 mitogen-activated protein kinase (p38MAPK).DATS-mediatedapoptosis induction and inhibition of HUVEC tube formation was partially but statistically significantly attenuated by pharmacologic inhibition of ERK1/2 but not JNK or p38MAPK. The present study demonstrates, for the first time, that DATS has the ability to inhibit angiogenic features of human endothelial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0163-5581
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
94-107
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16965246-Allyl Compounds, pubmed-meshheading:16965246-Angiogenesis Inhibitors, pubmed-meshheading:16965246-Apoptosis, pubmed-meshheading:16965246-Caspases, pubmed-meshheading:16965246-Cell Survival, pubmed-meshheading:16965246-Cells, Cultured, pubmed-meshheading:16965246-DNA Fragmentation, pubmed-meshheading:16965246-Dose-Response Relationship, Drug, pubmed-meshheading:16965246-Down-Regulation, pubmed-meshheading:16965246-Endothelial Cells, pubmed-meshheading:16965246-Garlic, pubmed-meshheading:16965246-Humans, pubmed-meshheading:16965246-Inhibitory Concentration 50, pubmed-meshheading:16965246-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16965246-Sulfides, pubmed-meshheading:16965246-Umbilical Veins, pubmed-meshheading:16965246-Vascular Endothelial Growth Factor A, pubmed-meshheading:16965246-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2006
pubmed:articleTitle
Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cells by causing Akt inactivation and down-regulation of VEGF and VEGF-R2.
pubmed:affiliation
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural