rg108 has been researched along with epigallocatechin-gallate* in 2 studies
2 other study(ies) available for rg108 and epigallocatechin-gallate
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Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells.
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. Topics: Animals; Anticarcinogenic Agents; Azacitidine; Catechin; Cell Line, Tumor; Cell Proliferation; Cytidine; Decitabine; DNA Methylation; Humans; Lung Neoplasms; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Neoplasm Transplantation; Phthalimides; Tryptophan; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays | 2014 |
Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines.
DNA methyltransferase inhibitors represent promising new drugs for cancer therapies. The first of these compounds (5-azacytidine, Vidaza) has recently been approved as an antitumor agent, and others are presently in various stages of their preclinical or clinical development. Most of the archetypal inhibitors have been established and characterized in different experimental systems, which has thus far precluded their direct comparison. We have now established defined experimental conditions that allowed a comparative analysis of the six most widely known DNA methyltransferase inhibitors: 5-azacytidine (5-aza-CR), 5-aza-2'-deoxycytidine (5-aza-CdR), zebularine, procaine, (-)-epigallocatechin-3-gallate (EGCG), and RG108. Of these, 5-aza-CR, 5-aza-CdR, zebularine, and EGCG were found to exhibit significant cytotoxicity in human cancer cell lines. 5-aza-CdR and EGCG were also found to be genotoxic, as evidenced by the induction of micronuclei. In addition, 5-aza-CR, 5-aza-CdR, zebularine, and RG108 caused concentration-dependent demethylation of genomic DNA, whereas procaine and EGCG failed to induce significant effects. Finally, the experiments in cancer cell lines were complemented by a cell-free in vitro assay with purified recombinant DNA methyltransferase, which indicated that RG108 is the only drug capable of direct enzyme inhibition. These results show a substantial diversity in the molecular activities of DNA methyltransferase inhibitors and provide valuable insights into the developmental potential of individual drugs. Topics: Azacitidine; Catechin; Cell Line, Tumor; Cytidine; Decitabine; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; Enzyme Inhibitors; Humans; Indoles; Jurkat Cells; Phthalimides; Procaine; Propionates; Tryptophan | 2006 |