Linked Life Data

20688834

Source:http://linkedlifedata.com/resource/pubmed/id/20688834

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2010-10-8
pubmed:abstractText
Sphingolipid metabolism is driven by inflammatory cytokines. These cascade of events include the activation of sphingosine kinase (SK), and subsequent production of the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). Overall, S1P is one of the crucial components in inflammation, making SK an excellent target for the development of new anti-inflammatory drugs. We have recently shown that SK inhibitors suppress colitis and hypothesize here that the novel SK inhibitor, ABC294640, prevents the development of colon cancer. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model, there was a dose-dependent decrease in tumor incidence with SK inhibitor treatment. The tumor incidence (number of animals with tumors per group) in the vehicle, ABC294640 (20 mg/kg) and ABC294640 (50 mg/kg) groups were 80, 40 and 30%, respectively. Tumor multiplicity (number of tumors per animal) also decreased from 2.1?±?0.23 tumors per animal in the AOM + DSS + vehicle group to 1.2?±?0 tumors per animal in the AOM + DSS + ABC294640 (20 mg/kg) and to 0.8?±?0.4 tumors per animal in the AOM + DSS + ABC294640 (50 mg/kg) group. Importantly, with ABC294640, there were no observed toxic side effects. To explore mechanisms, we isolated cells from the colon (CD45-, representing primarily colon epithelial cells) and (CD45+, representing primarily colon inflammatory cells) then measured known targets of SK that control cell survival. Results are consistent with the hypothesis that the inhibition of SK activity by our novel SK inhibitor modulates key pathways involved in cell survival and may be a viable treatment strategy for the chemoprevention colitis-driven colon cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-(4-chlorophenyl)-adamantane-1-carb..., http://linkedlifedata.com/resource/pubmed/chemical/Adamantane, http://linkedlifedata.com/resource/pubmed/chemical/Azoxymethane, http://linkedlifedata.com/resource/pubmed/chemical/Dextran Sulfate, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP..., http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group..., http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine kinase
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1787-93
pubmed:dateRevised
2011-10-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase.
pubmed:affiliation
Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina and Medical University of South Carolina, Columbia, SC 29208, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural