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Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells
- Source :
- Oncotarget
- Publication Year :
- 2014
-
Abstract
- The p53 protein ensures cellular fidelity by suppressing or killing cells under stresses that enhance the mutation rate. Evidence suggests that the p53 protein may also ensure the fidelity of the epigenome. In this study a group of drugs that alter the deoxycytosine methylation patterns in cellular DNA are shown to preferentially kill human and mouse cells that contain p53 mutations or deficiencies. These observations are extended to mice that contain p53 deficiencies or missense mutations in their genome, which are preferentially killed when compared to mice with a wild type p53 gene. This is also the case for human cancer cell xenografts containing p53 mutations, which preferentially are killed by these drugs when compared to similar tumors with wild type p53. The loss of p53 function enhances a synthetic lethality with drugs that block or alter the patterns of deoxycytidine methylation in the genome.
- Subjects :
- p53
Lung Neoplasms
Phthalimides
Synthetic lethality
Cytidine
Biology
medicine.disease_cause
Decitabine
Catechin
chemistry.chemical_compound
Mice
DNA methylation inhibitor
Cell Line, Tumor
medicine
Animals
Anticarcinogenic Agents
Humans
Zebularine
Gene
Cell Proliferation
Mice, Knockout
Mutation
FCDR
Wild type
Tryptophan
RG108
Methylation
Epigenome
DNA Methylation
Molecular biology
Xenograft Model Antitumor Assays
Mice, Inbred C57BL
Oncology
chemistry
DNA methylation
Azacitidine
Tumor Suppressor Protein p53
EGCG
Neoplasm Transplantation
Priority Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 5
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....7085a19fc4a939f40a4974580b02485b