Cover caption

Abstract

Histone deactylases (HDACs), which counteract the activity of histone acetyltransferases, remove acetyl groups from histones and other proteins such as transcription factors. Deacetylation makes the chromatin less accessible to the transcription machinery. Interestingly, the HDAC inhibitors seem to both activate and repress gene expression. These inhibitors are able induce growth arrest, differentiation and apoptosis in cancer cells. These widespread effects make it important to identify the relevant pathways targeted by the HDACi, which will aid in future drug development. Currently, there are multiple clinical trials testing a variety of HDAC inhibitors. In the current issue of Cancer Biology & Therapy, Zhang and colleagues follow up on data from a clinical trial that showed reduced expression of Aurora A, a mitotic kinase important for spindle formation, in response to HDAC inhibitor treatment. The cover of this month's issue of Cancer Biology & Therapy shows the effects of the HDACi, Depsipeptide FK228 (DP), on lung cancer cells. In the upper left hand corner is a mitotic figure from an untreated lung cancer culture. The remaining three aberrant mitotic figures are from lung cancer cultures treated with DP. The upper right and lower left figures show aberrant mitotic figures in which the centromeres (pink) fail to properly align at the metaphase plate. The figure in the bottom right corner shows a multipolar spindle from a DP treated lung cancer cell. The mitotic spindles are shown in green and chromosomes are stained blue. To find out more about how HDAC inhibitors work to inhibit Aurora A thereby inducing mitotic catastrophe see the paper by Zhang and colleagues.