Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azacitidine and decitabine are DNA methyltransferase inhibitors used to treat myelodysplastic syndromes and acute myeloid leukemias. To further characterize different mechanisms between these two agents, cellular extracts from leukemic cells untreated or treated with either drug were analyzed using 2D electrophoresis. Numerous differentially expressed proteins were identified with MALDI-TOF/TOF-MS. Cyclophilin A, Catalase, Nucleophosmin and PCNA were decreased exclusively by azacitidine, TCP1 and hnRNP A2/B1 by both drugs; alpha-Enolase and Peroxiredoxin-1 by decitabine. Interestingly, the expression of the proinflammatory protein Cyclophilin A, also suggested as marker of cell necrosis, was stimulated by decitabine. Finally, a comprehensive pathway analysis of data highlighted a relationship between the identified proteins and potential effectors.
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PMID:Proteomic analysis identifies differentially expressed proteins in AML1/ETO acute myeloid leukemia cells treated with DNMT inhibitors azacitidine and decitabine. 2223 Feb 98

Chronic inflammation is strongly associated with an increased risk of developing colorectal cancer. DNA hypermethylation of CpG islands alters the expression of genes in cancer cells and plays an important role in carcinogenesis. Chronic inflammation is also associated with DNA methylation alterations and in a mouse model of inflammation-induced colon tumorigenesis, we previously demonstrated that inflammation-induced tumours have 203 unique regions with DNA hypermethylation compared to uninflamed epithelium. To determine if altering inflammation-induced DNA hypermethylation reduces tumorigenesis, we used the same mouse model and treated mice with the DNA methyltransferase (DNMT) inhibitor decitabine (DAC) throughout the tumorigenesis time frame. DAC treatment caused a significant reduction in colon tumorigenesis. The tumours that did form after DAC treatment had reduced inflammation-specific DNA hypermethylation and alteration of expression of associated candidate genes. When compared, inflammation-induced tumours from control (PBS-treated) mice were enriched for cell proliferation associated gene expression pathways whereas inflammation-induced tumours from DAC-treated mice were enriched for interferon gene signatures. To further understand the altered tumorigenesis, we derived tumoroids from the different tumour types. Interestingly, tumoroids derived from inflammation-induced tumours from control mice maintained many of the inflammation-induced DNA hypermethylation alterations and had higher levels of DNA hypermethylation at these regions than tumoroids from DAC-treated mice. Importantly, tumoroids derived from inflammation-induced tumours from the DAC-treated mice proliferated more slowly than those derived from the inflammation-induced tumours from control mice. These studies suggest that inhibition of inflammation-induced DNA hypermethylation may be an effective strategy to reduce inflammation-induced tumorigenesis.
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PMID:DNA methyltransferase inhibition reduces inflammation-induced colon tumorigenesis. 3124 Sep 97