Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides.

Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Research Abstract Details 

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Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Abstract Text:

Christine B Yoo,Shinwu Jeong,Gerda Egger,Gangning Liang,Pasit Phiasivongsa,Chunlin Tang,Sanjeev Redkar,Peter A Jones,

The major goal of epigenetic therapy is to reverse aberrant promoter hypermethylation and restore normal function of tumor suppressor genes by the use of chromatin-modifying drugs. Decitabine, or 5-aza-2'-deoxycytidine (5-aza-CdR), is a well-characterized drug that is now Food and Drug Administration approved for the treatment of myelodysplastic syndrome. Although 5-aza-CdR is an extremely potent inhibitor of DNA methylation, it is subject to degradation by hydrolytic cleavage and deamination by cytidine deaminase. We show that short oligonucleotides containing a 5-aza-CdR can also inhibit DNA methylation in cancer cells at concentrations comparable with 5-aza-CdR. Detailed studies with S110, a dinucleotide, showed that it works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. Stability of the triazine ring in aqueous solution was not improved in the S110 dinucleotide; however, deamination by cytidine deaminase was dramatically decreased. This is the first demonstration of the use of short oligonucleotides to provide effective delivery and cellular uptake of a nucleotide drug and protection from enzymatic degradation. This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics.

Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Publishing Authors By Initials

CB Yoo,S Jeong,G Egger,G Liang,P Phiasivongsa,C Tang,S Redkar,PA Jones,

For similar neoplasms: neoplasms by site: urogenital neoplasms: urologic neoplasms: urinary bladder neoplasms research abstracts see: neoplasms: neoplasms by site: urogenital neoplasms: urologic neoplasms: urinary bladder neoplasms research

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Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 67

Page Numbers: 6400-8

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Jul

YEAR: 2007

Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Keywords Mesh Terms:

KEYWORDS: Urinary Bladder Neoplasms

MESH TERMS: drug therapy

Chemical & Substance for Abstract: Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides. Information

Substance Name: Azacitidine

Registry Number: 320-67-2

Grant and Affiliation Information for Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotides.

AFFILIATION: Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA82422

ACRONYM: CA

MEDLINETA: Cancer Res

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