DNA hypermethylation as a chemotherapy target

Juan Ren, Brahma N. Singh, Qiang Huang, Zongfang Li, Ya Gao, Prachi Mishra, Yi L. Hwa, Jinping Li, Sean Christopher Dowdy, Shi Wen Jiang

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Epigenetics refers to partially reversible, somatically inheritable, but DNA sequence-independent traits that modulate gene expression, chromatin structure, and cell functions such as cell cycle and apoptosis. DNA methylation is an example of a crucial epigenetic event; aberrant DNA methylation patterns are frequently found in human malignancies. DNA hypermethylation and the associated expression silencing of tumor suppressor genes represent a hallmark of neoplastic cells. The cancer methylome is highly disrupted, making DNA methylation an excellent target for anti-cancer therapies. Several small synthetic and natural molecules, are able to reverse the DNA hypermethylation through inhibition of DNA methyltransferase (DNMT). DNMT is the enzyme catalyzing the transfer of methyl groups to cytosines in genomic DNA. These reagents are studied intensively in cell cultures, animal models, and clinical trials for potential anti-cancer activities. It was found that accompanying DNA demethylation is a dramatic reactivation of the silenced genes and inhibition of cancer cell proliferation, promotion of cell apoptosis, or sensitization of cells to other chemotherapeutic reagents. During the last few decades, an increasing number of DNMT inhibitors (DNMTi) targeting DNA methylation have been developed to increase efficacy with reduced toxicity. This review provides an update on new findings on cancer epigenetic mechanisms, the development of new DNMTi, and their application in the clinical setting. Current challenges, potential solutions, and future directions concerning the development of DNMTi are also discussed in this review.

Original languageEnglish (US)
Pages (from-to)1082-1093
Number of pages12
JournalCellular Signalling
Volume23
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Drug Therapy
DNA Methylation
DNA
Methyltransferases
Epigenomics
Neoplasms
Apoptosis
Neoplasm Genes
Cytosine
Tumor Suppressor Genes
Chromatin
Cell Cycle
Animal Models
Cell Culture Techniques
Cell Proliferation
Clinical Trials
Gene Expression
Enzymes
Therapeutics

Keywords

  • Cancer
  • DNA methylation
  • DNA methyltranferases
  • DNMT inhibitors
  • Hypermethylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Ren, J., Singh, B. N., Huang, Q., Li, Z., Gao, Y., Mishra, P., ... Jiang, S. W. (2011). DNA hypermethylation as a chemotherapy target. Cellular Signalling, 23(7), 1082-1093. https://doi.org/10.1016/j.cellsig.2011.02.003

DNA hypermethylation as a chemotherapy target. / Ren, Juan; Singh, Brahma N.; Huang, Qiang; Li, Zongfang; Gao, Ya; Mishra, Prachi; Hwa, Yi L.; Li, Jinping; Dowdy, Sean Christopher; Jiang, Shi Wen.

In: Cellular Signalling, Vol. 23, No. 7, 07.2011, p. 1082-1093.

Research output: Contribution to journalArticle

Ren, J, Singh, BN, Huang, Q, Li, Z, Gao, Y, Mishra, P, Hwa, YL, Li, J, Dowdy, SC & Jiang, SW 2011, 'DNA hypermethylation as a chemotherapy target', Cellular Signalling, vol. 23, no. 7, pp. 1082-1093. https://doi.org/10.1016/j.cellsig.2011.02.003
Ren J, Singh BN, Huang Q, Li Z, Gao Y, Mishra P et al. DNA hypermethylation as a chemotherapy target. Cellular Signalling. 2011 Jul;23(7):1082-1093. https://doi.org/10.1016/j.cellsig.2011.02.003
Ren, Juan ; Singh, Brahma N. ; Huang, Qiang ; Li, Zongfang ; Gao, Ya ; Mishra, Prachi ; Hwa, Yi L. ; Li, Jinping ; Dowdy, Sean Christopher ; Jiang, Shi Wen. / DNA hypermethylation as a chemotherapy target. In: Cellular Signalling. 2011 ; Vol. 23, No. 7. pp. 1082-1093.
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