What is HDAC?

HDAC (Histone deacetylases) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on ahistone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone acetyltransferase. In general, the acetylation of histone facilitates the dissociation of DNA from histone octamer and the relaxation of nucleosome structure, which enables various transcription factors and co-transcription factors to specifically bind to DNA binding sites and activate the transcription of genes. In the nucleus, the process of histone acetylation and histone deacetylation is in a dynamic equilibrium and is regulated by HAT and HDAC.

HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins. The acetyl group of acetyl coenzyme A was transferred to the specific lysine residue of histone amino terminal by HAT. The histone was deacetylated and tightly bound to the negatively charged DNA. The chromatin was compact and curled and the transcription of the gene was inhibited. Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily.

HDAC Inhibitor—Panobinostat

Panobinostat (LBH589) is a novel, broad-spectrum HDAC inhibitor with IC50 of 5 nm.

Panobinostat In vitro studies:

LBH589 induced apoptosis of MOLT-4 and Reh cells in a time and dose-dependent manner. Moreover, LBH 589 was more effective on MOLT-4 cells than on Reh cells. LBH589 inhibited the growth of MOLT-4 and Reh cells in a dose-dependent manner for 48 hours. Compared with the control group, the number of cells treated with LBH589 increased by 2 to 3 times in the G 2 / M phase of cell cycle. LBH589 is associated with acetylation of histone H3K9 and H4K8. LBH589 also reduced the expression of c-Myc. LBH589 also enhanced the expression of p21. Reh cells were treated with the lowest dose of LBH589 (10 nm), which initially enhanced the expression of c-Myc, and then decreased the expression of c-Myc. In addition, LBH 589 promotes the apoptosis of mRNA and the increase of DNA repair genes.

Panobinostat In vivo studies:

The effect of LBH589 on animal models of lung cancer and mesothelioma significantly decreased tumor growth. Compared with the control group, the average reduction was 62%. The effect of LBH589 on immunoactive mice was similar to that on severe combined immunodeficient mice, indicating that the inhibition of tumor growth by LBH589 was independent of immunology. LBH589 was injected intraperitoneally at a dose of 20 mg/kg for 5 days a week, resulting in an average decrease of 70 kW in tumor growth at the end of the experiment. Compared with the corresponding control group, the tumour induced by LBH 589 decreased 53%, the tumor induced by BK-T decreased 81%, the tumor induced by RG-1 decreased 76%, and the tumor induced by H69 decreased 70%.

Author's Bio: 

Histone deacetylases (HDACs), that may be called protein deacetylases (PDAC) as some of their targets are non-histone proteins, are a family of eleven zinc-dependent enzymes that have gained major interest as therapeutic targets, mainly in cancer research. BOC Sciences offers quality HDAC products for research communities