HDAC Inhibitors and Heat Shock Proteins (Hsps)

Epigenetic alterations, including DNA acetylation, hypermethylation and hypomethylation, and the associated transcriptional changes of the affected genes are central to the evolution and progression of various human cancers, including pancreatic cancer. Cancer-associated epigenetic alterations are attractive therapeutic targets because such epigenetic alterations, unlike genetic changes, are potentially reversible. Several drugs that target epigenetic alterations, including inhibitors of histone deacetylase (HDAC) and DNA methyltransferase (DNMT), are currently approved for treatment of hematological malignancies and are available for clinical investigation in solid tumors. Histone deacetylases (HDACs) is well known to be associated with tumorigenesis through epigenetic regulation. HDACs comprise an ancient family of enzymes that play crucial roles in numerous biological processes and HDACs are found to be over expressed in many tumor types. Its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. In addition, the activity of heat shock proteins (Hsps) can be regulated by HDACs. Hsps exist in many types of cells and these proteins can prevent aggregation and formation of toxic inclusion. Hsps are major molecular chaperones in prokaryotic and eukaryotic cells. This review summarizes mechanisms of histone deacetylase inhibitors action on Hsps and will describe the regulation of major cellular chaperones and heat shock factors by HDAC-mediated deacetylation.