Creation of a histone deacetylase 6 inhibitor and its biological effects [corrected].

We report the development of a potent, selective histone deacetylase 6 (HDAC6) inhibitor. This HDAC6 inhibitor blocks growth of normal and transformed cells but does not induce death of normal cells. The HDAC6 inhibitor alone is as effective as paclitaxel in anticancer activity in tumor-bearing mice.

Development of a histone deacetylase 6 inhibitor and its biological effects.

Development of isoform-selective histone deacetylase (HDAC) inhibitors is important in elucidating the function of individual HDAC enzymes and their potential as therapeutic agents. Among the eleven zinc-dependent HDACs in humans, HDAC6 is structurally and functionally unique. Here, we show that a hydroxamic acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2-oxoethyl)benzamide (HPOB) selectively inhibits HDAC6 catalytic activity in vivo and in vitro.

Mechanisms of resistance to histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors are a new class of anticancer agents. HDAC inhibitors induce acetylation of histones and nonhistone proteins which are involved in regulation of gene expression and in various cellular pathways including cell growth arrest, differentiation, DNA damage and repair, redox signaling, and apoptosis (Marks, 2010). The U.

Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors.

Histone deacetylase inhibitors (HDACi) are a new group of anticancer drugs with tumor selective toxicity. Normal cells are relatively resistant to HDACi-induced cell death compared with cancer cells. Previously, we found that vorinostat induces DNA breaks in normal and transformed cells, which normal but not cancer cells can repair.

Suberoylanilide hydroxamic acid limits migration and invasion of glioma cells in two and three dimensional culture.

High grade gliomas are aggressive cancers that are not well addressed by current chemotherapies, in large measure because these drugs do not curtail the diffuse invasion of glioma cells into brain tissue surrounding the tumor. Here, we investigate the effects of suberoylanilide hydroxamic acid (SAHA) on glioma cells in 2D and 3D in vitro assays, as SAHA has previously been shown to significantly increase apoptosis, decrease proliferation, and interfere with migration in other cell lines. We find that SAHA has significant independent effects on proliferation, migration, and invasion.

Polyelectrolyte microcapsule interactions with cells in two- and three-dimensional culture.

Microcapsules fabricated by layer-by-layer self-assembly have unique physicochemical properties that make them attractive for drug delivery applications. This study chiefly investigated the biocompatibility of one of the most stable types of microcapsules, those composed of poly-(sodium 4-styrene sulfonate) [PSS] and poly-(allylamine hydrochloride) [PAH], with cells cultured on two-dimensional (2D) substrates and in three-dimensional (3D) matrices. C6 glioma and 3T3 fibroblast cell morphology was observed after 24h of co-culture with PSS/PAH microcapsules on a 2D substrate.