Priority Research Papers:
Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells
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1Rugters Cancer Institute of New Jersey, New Brunswick, New Jersey
2Department of Pediatrics, Rutgers New Jersey Medical School, Piscataway, New Jersey
3The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey
Dr. Arnold Levine, email: [email protected]
Keywords: FCDR, Decitabine, Zebularine, EGCG, RG108, DNA methylation inhibitor, p53
Received: April 26, 2014 Accepted: September 05, 2014 Published: September 10, 2014
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.
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