What is a pan HDAC inhibitor?
The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis.
What is HDAC in cancer?
Abstract. Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in both cancer initiation and cancer progression.
What is the role of DAC inhibitor in cancer treatment?
HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death. Moreover, they reduce angiogenesis and modulate immune response. Hypothesis of “epigenetic vulnerability of cancer cells”, which has been proposed by Dawson and Kouzarides , is a cause of relative specificity of HDAC inhibitors.
What do histone deacetylases do?
Histone deacetylases (HDACs) are enzymes that remove acetyl groups from lysine residues in the NH2 terminal tails of core histones, resulting in a more closed chromatin structure and repression of gene expression. These enzymes are dependent on NAD for their activity and do not contain zinc as do the other HDACs.
How do HDAC inhibitors work?
HDACs can act as transcription repressors, due to histone deacetylation, and consequently promote chromatin condensation. HDAC inhibitors (HDACi) selectively alter gene transcription, in part, by chromatin remodeling and by changes in the structure of proteins in transcription factor complexes (Gui et al., 2004).
How do HDAC work?
What is the mechanism of action of Apicidin?
Apicidin inhibits the activity of several subclasses of HDACs (HDAC2, HDAC3, and HDAC8). Romidepsin is an HDAC2 inhibitor that plays a crucial role in cognitive loss in AD.29,82 These inhibitors might be potential tools, since HDAC2 and HDAC3 are two of the most highly expressed HDACs in the substantia nigra.
Is Apicidin a good inhibitor of HDA?
The results presented here clearly show that apicidin as well as the known mammalian HDA inhibitors, HC-toxin and trichostatin, are potent inhibitors of parasite HDA. The 2-amino-8-oxo-decanoic acid moiety of apicidin is unique relative to related tetrapeptides where an epoxide is required for biological activity.
Does Apicidin affect dendritic cell maturation?
Apicidin is a fungal metabolite shown to exhibit anti-proliferative, anti-invasive, and anti-inflammatory properties by the inhibition of histone deacetylase (HDAC). However, the effects of apicidin on the maturation and immunostimulatory function of dendritic cells (DCs) remain unknown.
Does Apicidin kill apicomplexan parasites?
In this paper, a novel natural product, apicidin, that has broad spectrum activity against the Apicomplexan parasites is described, and experimental evidence that demonstrates that this compound kills parasites by inhibiting histone deacetylas…