Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy.

摘要: The deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) has been used as a drug in part of cancer therapy. However, because its incorporation into DNA during synthesis, 5-aza-dC can cause damage, mutagenesis, and cytotoxicity. In view the adverse effects 5-aza-dC, DNMT-targeted inhibition may be more effective approach than treatment with 5-aza-dC. To address possibility therapy, we compared small interfering ribonucleic acids (siRNAs) specific for DNMT1 or DNMT3b on transcription, cell growth, damage gastric cells. We found that DNMT1-targeted induced re-expression reversed methylation five (CDKN2A, RASSF1A, HTLF, RUNX3, AKAP12B) out seven genes examined, reactivated demethylated all genes. contrast, siRNAs did not show any effect. Furthermore, double knockdown synergistic effect gene demethylation. addition, showed an inhibitory proliferation cells induction death without evidence whereas caused demonstrated by comet assay. These results provide rationale development strategy epigenetic