Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/228
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dc.contributor.authorSampathkumar, Srinivasa-Gopalan-
dc.date.accessioned2014-11-21T09:15:40Z-
dc.date.available2014-11-21T09:15:40Z-
dc.date.issued2008-12-
dc.identifier.urihttp://hdl.handle.net/123456789/228-
dc.description.abstractPer-butanoylated N-acetyl-D-mannosamine (Bu(4)ManNAc), a SCFA-hexosamine cancer drug candidate with activity manifest through intact n-butyrate-carbohydrate linkages, reduced the invasion of metastatic MDA-MB-231 breast cancer cells unlike per-butanoylated-D-mannose (Bu(5)Man), a clinically tested compound that did not alter cell mobility. To gain molecular-level insight, therapeutic targets implicated in metastasis were investigated. The active compound Bu(4)ManNAc reduced both MUC1 expression and MMP-9 activity (via down-regulation of CXCR4 transcription), whereas "inactive" Bu(5)Man had counterbalancing effects on these oncogenes. This divergent impact on transcription was linked to interplay between HDACi activity (held by both Bu(4)ManNAc and Bu(5)Man) and NF-kappaB activity, which was selectively down-regulated by Bu(4)ManNAc. Overall, these results establish a new therapeutic end point (control of invasion) for SCFA-hexosamine hybrid molecules, define relative contributions of molecular players involved in cell mobility and demonstrate that Bu(4)ManNAc breaks the confounding link between beneficial HDACi activity and the simultaneous deleterious activation of NF-kappaB often found in epigenetic drug candidates.en_US
dc.publisherAmerican Chemical Societyen_US
dc.subjectChemical biologyen_US
dc.titleTargeting pro-invasive oncogenes with short chain fatty acid-hexosamine analogues inhibits the mobility of metastatic MDA-MB-231 breast cancer cellsen_US
dc.contributor.coauthorAich, Udayanath-
dc.contributor.coauthorWeier, Christopher A.-
dc.contributor.coauthorWang, Jean J-
dc.contributor.coauthorChoi, Sean S-
dc.contributor.coauthorWen, Mary M-
dc.contributor.coauthorMaisel, Katharina-
dc.contributor.coauthorYarema, Kevin J-
dc.keywordPer-butanoylated N-acetyl-D-mannosamineen_US
dc.journalJournal of Medicinal Chemistryen_US
dc.volumeno51en_US
dc.issueno24en_US
dc.pages8135-8147en_US
Appears in Collections:Chemical Glycobiology, Publications



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