Article ; Online: Synergistic anti-breast cancer effect of a combined treatment with the methyl donor S-adenosyl methionine and the DNA methylation inhibitor 5-aza-2'-deoxycytidine.
2014 Volume 35, Issue 1, Page(s) 138–144
Abstract: DNA-demethylating agents activate tumor suppressor genes that are silenced by DNA methylation in cancer and are therefore emerging as a novel approach to cancer therapy. 5-azacytidine (VIDAZA), the first representative of this class of drugs was approved ...
Abstract | DNA-demethylating agents activate tumor suppressor genes that are silenced by DNA methylation in cancer and are therefore emerging as a novel approach to cancer therapy. 5-azacytidine (VIDAZA), the first representative of this class of drugs was approved for treatment of myelodysplastic syndromes and is currently being tested on other cancers including solid tumors. However, 5-azacytidine or its deoxy-analog, 5-aza-2'-deoxycytidine (5-azaCdR) could also induce methylated prometastatic genes by DNA demethylation and induce cancer cell invasiveness. Since 5-azacytidine is a potent cancer growth inhibitor, we tested whether combining it with a DNA-methylating agent, the methyl donor S-adenosyl methionine (SAM), would block the adverse demethylating activity of 5-azaCdR while maintaining its growth suppression effects. We show here using several invasive and non-invasive breast cancer cell lines that SAM inhibits global- and gene-specific demethylation induced by 5-azaCdR, prevents 5-azaCdR activation of prometastatic genes uPA and MMP2, resulting in inhibition of cell invasiveness while augmenting the growth inhibitory effects of 5-azaCdR and its effects on tumor suppressor genes. Combination of drugs acting on the DNA methylation machinery at different levels is proposed as a new strategy for epigenetic therapy of cancer. |
---|---|
MeSH term(s) | Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Azacitidine/analogs & derivatives ; Azacitidine/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; DNA Methylation/drug effects ; Drug Synergism ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, Tumor Suppressor ; Humans ; MCF-7 Cells/drug effects ; Matrix Metalloproteinase 2/genetics ; S-Adenosylmethionine/pharmacology ; Urokinase-Type Plasminogen Activator/genetics ; Urokinase-Type Plasminogen Activator/metabolism |
Chemical Substances | decitabine (776B62CQ27) ; S-Adenosylmethionine (7LP2MPO46S) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Azacitidine (M801H13NRU) |
Language | English |
Publishing date | 2014-01 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 603134-1 |
ISSN | 1460-2180 ; 0143-3334 |
ISSN (online) | 1460-2180 |
ISSN | 0143-3334 |
DOI | 10.1093/carcin/bgt284 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 1558: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.