BACKGROUND Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. METHODOL...

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb hom...

Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTC...

Histone deacetylases (HDACs) catalyze the removal of acetyl groups from histones and contribute to transcriptional repression. In addition, the HDAC inhibitors induce apoptosis in cancer cells through alterations in histone acetylation and activation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) apoptotic pathway. Lysophosphatidic acid (LPA) is a growth factor that prom...

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC and most show a poor selectivity profile, side effects, in particular hydroxamic-acid-based lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid is highly regarded field medi...

Histone deacetylase (HDAC) inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials...

Excessive accumulation of extracellular matrix (ECM) in the kidneys and epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells contributes to the renal fibrosis that is associated with diabetic nephropathy. Histone deacetylase (HDAC) determines the acetylation status of histones and thereby controls the regulation of gene expression. This study examined the effect of HDAC ...

Histone deacetylase (HDAC) inhibitors are promising new epi-drugs, but the presence of both class I and class II enzymes in HDAC complexes precludes a detailed elucidation of the individual HDAC functions. By using the class II-specific HDAC inhibitor MC1568, we separated class I- and class II-dependent effects and defined the roles of class II enzymes in muscle differentiation in cultured cell...

Noh H, Oh EY, Seo JY, Yu MR, Kim YO, Ha H, Lee HB. Histone deacetylase-2 is a key regulator of diabetesand transforming growth factor1-induced renal injury. Am J Physiol Renal Physiol 297: F729 –F739, 2009. First published June 24, 2009; doi:10.1152/ajprenal.00086.2009.—Excessive accumulation of extracellular matrix (ECM) in the kidneys and epithelial-tomesenchymal transition (EMT) of renal tub...

Histone deacetylase (HDAC)-6 was recently identified as a dual substrate, possibly multisubstrate, deacetylase that can act both on acetylated histone tails and on alpha-tubulin acetylated on Lys40. HDAC-6 is unique among deacetylases in having two hdac domains, and we have used this enzyme as a useful model to dissect the structural requirements for the deacetylation reaction. In this report, ...