Protein arginine deiminase 4: a target for an epigenetic cancer therapy
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2011-02-01Keywords
AmidinesAnimals
Antibiotics, Antineoplastic
Antigens, CD38
Antineoplastic Agents
Cell Differentiation
Cell Line, Tumor
Cell Survival
Cyclin-Dependent Kinase Inhibitor p21
Doxorubicin
Drug Synergism
Enzyme Inhibitors
Epigenomics
Gene Expression Regulation, Neoplastic
Humans
Hydrolases
Neoplasms
Protein arginine deiminase
Haloacetamidine
Inhibition
HL-60
Epigenetics
Citrulline
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Neoplasms
Therapeutics
Metadata
Show full item recordAbstract
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted the important role that epigenetics plays in human diseases, and suggested that the factors controlling gene expression are novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine, two potent PAD4 inhibitors, display micromolar cytotoxic effects towards several cancerous cell lines (HL-60, MCF7 and HT-29); no effect was observed in noncancerous lines (NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally, these compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together, these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease.Source
Cell Mol Life Sci. 2011 Feb;68(4):709-20. doi: 10.1007/s00018-010-0480-x. Link to article on publisher's site. Epub 2010 Aug 13.DOI
10.1007/s00018-010-0480-xPermanent Link to this Item
http://hdl.handle.net/20.500.14038/50046Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1007/s00018-010-0480-x