DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer

Title:DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer

Volume: 13 Issue: 4

Author(s): Varinder Singh, Prince Sharma and Neena Capalash

Affiliation:

Keywords: Cancer, DNA methylation, methylation inhibition, reexpression, therapy, tumor suppressor genes.

Abstract: DNA methylation is an epigenetic modification involved in gene expression regulation. In cancer, the DNA methylation pattern becomes aberrant, causing an array of tumor suppressor genes to undergo promoter hypermethylation and become transcriptionally silent. Reexpression of methylation silenced tumor suppressor genes by inhibiting the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) has emerged as an effective strategy against cancer. The expression of DNA methyltransferase 1 (DNMT1) being high in S-phase of cell cycle makes it a specific target for methylation inhibition in rapidly dividing cells as in cancer. This review discusses nucleoside analogues (azacytidine, decitabine, zebularine, SGI-110, CP-4200), non-nucleoside ihibitors both synthetic (hydralazine, RG108, procaine, procainamide, IM25, disulfiram) and natural compounds (curcumin, genistein, EGCG, resveratrol, equol, parthenolide) which act through different mechanisms to inhibit DNMTs. The issues of bioavailability, toxicity, side effects, hypomethylation resistance and combinatorial therapies have also been highlighted.

Cite this article as:

Singh Varinder, Sharma Prince and Capalash Neena, DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer, Current Cancer Drug Targets 2013; 13 (4) . https://dx.doi.org/10.2174/15680096113139990077