BACKGROUND: Despite recent success toward discovery of more effective anticancer drugs, chemoresistance remains a major cause of treatment failure. There is emerging evidence that epigenetics plays a key role in the development of the resistance. Epigenetic regulators such as histone acetyltransferases (HATs) and histone deacetylases (HDACs) play an important role in gene expression. The latter are found to be commonly linked with many types of cancers and influence cancer development. Overall, histone acetylation is being investigated as a therapeutic target because of its importance in regulating gene expression. This review summarizes mechanisms of the anticancer effects of histone deacetylase (HDAC) inhibitors and the results of clinical studies. RESULTS: Different HDAC inhibitors induce cancer cell death by different mechanisms that include changes in gene expression and alteration of both histone and non-histone proteins. Enhanced histone acetylation in tumors results in modification of expression of genes involved in cell signaling. Inhibition of HDACs causes changed expression in 2-10 % of genes involved in important biological processes. The results of experiments and clinical studies demonstrate that combination of HDAC inhibitors with some anticancer drugs have synergistic or additive effects. CONCLUSIONS: Even though many biological effects of HDAC inhibitors have been found, most of the mechanisms of their action remain unclear. In addition, their use in combination with other drugs and the combination regime need to be investigated. The discovery of predictive factors is also necessary. Finally, a key question is whether the pan-HDAC inhibitors or the selective inhibitors will be more efficient for different types of cancers.

• MeSH
• Apoptosis drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Histone Deacetylase Inhibitors administration & dosage   pharmacology   MeSH
• Cell Cycle Checkpoints drug effects   MeSH
• Humans MeSH
• Neoplasms drug therapy   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Signal Transduction drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Lactoferrin, a globular glycoprotein, is an important component of saliva. It shows an antibacterial, anticancerogenic and anti-inflammatory activity. The aim of this study was to develop a method of isolation of lactoferrin from human saliva using ion exchange chromatography in a monolithic column and spectrometric detection with Pyrogallol Red by the Bradford and biuret methods. The calibration curve for lactoferrin was linear in the range 0.06–62.5 μg ml–1, limit of detection 0.01 μg ml–1. The lactoferin concentration in saliva of healthy subjects was 42±4 μg mg–1. Patient with celiac disease showed 2.5x times higher concentration of lactoferrin compared with healthy subjects.

• MeSH
• Chromatography, Ion Exchange * methods   instrumentation   utilization   MeSH
• Chromatography, Liquid * methods   instrumentation   utilization   MeSH
• Adult MeSH
• Lactoferrin * analysis   MeSH
• Humans MeSH
• Limit of Detection * MeSH
• Analytic Sample Preparation Methods MeSH
• Young Adult MeSH
• Saliva * MeSH
• Spectrophotometry, Ultraviolet MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH