Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs.

Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Research Abstract Details 

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Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Abstract Text:

Srinivasa-Gopalan Sampathkumar,Mark B Jones,M Adam Meledeo,Christopher T Campbell,Sean S Choi,Kaoru Hida,Prasra Gomutputra,Anthony Sheh,Tim Gilmartin,Steven R Head,Kevin J Yarema,

Short-chain fatty acid (SCFA)-carbohydrate hybrid molecules that target both histone deacetylation and glycosylation pathways to achieve sugar-dependent activity against cancer cells are described in this article. Specifically, n-butyrate esters of N-acetyl-D-mannosamine (But4ManNAc, 1) induced apoptosis, whereas corresponding N-acetyl-D-glucosamine (But4GlcNAc, 2), D-mannose (But5Man, 3), or glycerol (tributryin, 4) derivatives only provided transient cell cycle arrest. Western blots, reporter gene assays, and cell cycle analysis established that n-butyrate, when delivered to cells via any carbohydrate scaffold, functioned as a histone deacetylase inhibitor (HDACi), upregulated p21WAF1/Cip1 expression, and inhibited proliferation. However, only 1, a compound that primed sialic acid biosynthesis and modulated the expression of a different set of genes compared to 3, ultimately killed the cells. These results demonstrate that the biological activity of butyrate can be tuned by sugars to improve its anticancer properties.

Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Publishing Authors By Initials

SG Sampathkumar,MB Jones,MA Meledeo,CT Campbell,SS Choi,K Hida,P Gomutputra,A Sheh,T Gilmartin,SR Head,KJ Yarema,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Chemistry & biology

VOLUME: 13

Page Numbers: 1265-75

Journal Abbreviation: Chem. Biol.

ISSN: 1074-5521

DAY: 3

MONTH: Dec

YEAR: 2006

Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Information

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LANGUAGE: eng

NlmUniqueID: 9500160

Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs. Information

Substance Name: N-acetylmannosamine

Registry Number: 4773-29-9

Grant and Affiliation Information for Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of butyrate-carbohydrate cancer prodrugs.

AFFILIATION: Whiting School of Engineering, Clark Hall 106A, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.

Country: England

AGENCY: United States NIGMS

GRANT: GM62116

ACRONYM: GM

MEDLINETA: Chem Biol

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