GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Höglund, A, Nilsson, LM, Forshell, LP, Maclean, KH and Nilsson, JA (2009) Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine. Blood 113:4281-8


Decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53(-/-) mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.


PubMed Online version:10.1182/blood-2008-10-183475


Aneuploidy; Animals; Antimetabolites, Antineoplastic/pharmacology; Apoptosis/drug effects; Azacitidine/analogs & derivatives; Azacitidine/pharmacology; Blotting, Western; Burkitt Lymphoma/metabolism; Burkitt Lymphoma/pathology; Burkitt Lymphoma/virology; Cell Cycle; DNA Damage; DNA Methylation; DNA Modification Methylases/antagonists & inhibitors; DNA, Neoplasm/drug effects; Embryo, Mammalian; Epstein-Barr Virus Infections/genetics; Epstein-Barr Virus Infections/pathology; Epstein-Barr Virus Infections/virology; Fibroblasts/cytology; Fibroblasts/metabolism; Herpesvirus 4, Human/isolation & purification; Humans; Kidney/cytology; Kidney/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mutation/genetics; Proto-Oncogene Proteins c-myc/physiology; Tumor Suppressor Protein p53/metabolism