Development of curcumin as an epigenetic agent.

The clinical benefits of curcumin as a single agent were demonstrated in patients with advanced pancreatic cancer in a phase 2 study despite pharmacokinetic analysis showing a much lower plasma concentration of curcumin in humans than in vitro. The diverse and broad biological activities of curcumin are mediated through direct interaction of curcumin with target proteins as well as epigenetic modulation of target genes, supported by evidence that curcumin modulates gene expression in a time- and concentration-dependent manner in human cancer cells. This review delineates the novel mechanisms of curcumin as an epigenetic agent through its interaction with histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and microRNAs. Accumulating data support curcumin's functionality in modulating multiple biological processes at low concentrations through its activity as an epigenetic agent. The development of curcumin as an epigenetic agent warrants further preclinical and clinical studies to explore its diversity and efficacy in cancer treatment and in combination with other anticancer agents.