DNA Methyltransferase-1 Inhibitors as Epigenetic Therapy for Cancer

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

Journal Name: Current Cancer Drug Targets

Volume 13 , Issue 4 , 2013

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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.

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

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2013
Page: [379 - 399]
Pages: 21
DOI: 10.2174/15680096113139990077
Price: $58

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