title: Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells.
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.
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Department of Pediatrics, Rutgers New Jersey Medical School, Piscataway, New Jersey.
authors.forename: Lan
authors.initials: L
authors.lastname: Yi
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Department of Pediatrics, Rutgers New Jersey Medical School, Piscataway, New Jersey.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Rugters Cancer Institute of New Jersey, New Brunswick, New Jersey. Department of Pediatrics, Rutgers New Jersey Medical School, Piscataway, New Jersey. The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey.
authors.forename: Arnold
authors.initials: A
authors.lastname: Levine
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009368:Neoplasm Transplantation; D010797:Phthalimides / Q000494:pharmacology; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; D010797:Phthalimides; C503639:RG108; D016159:Tumor Suppressor Protein p53; D003562:Cytidine; D000077209:Decitabine; C009131:pyrimidin-2-one beta-ribofuranoside; D014364:Tryptophan; D002392:Catechin; C045651:epigallocatechin gallate; D001374:Azacitidine