What does an HDAC inhibitor do?
Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells.
Which type of cancer is targeted in histone deacetylase inhibitor HDAC therapy select all that apply?
Although hematological malignancies remain the major clinical targets for HDACi, several have now been trialed against more common solid tumors, including lung, breast and prostate cancer (Tables 1 and 2).
How is HDAC activated?
Whilst the structures of HDACs 1 and 3 in complex with their cognate co-repressors, along with functional studies, have established that these complexes are activated by inositol phosphates3, the exact mechanism through which inositol phosphates activate HDACs remains unclear.
What effect would a HDAC inhibitor have on the target cells?
HDAC inhibitors increase accumulation of acetylated histones, resulting in decreased availability of nuclear DNA to bind to transcription factors. The decrease in transcription decreases intracellular protein levels, ultimately producing cell cycle arrest and apoptosis.
What drugs are HDAC inhibitors?
To date, four HDAC inhibitors, Vorinostat, Romidepsin, Panobinostat, and Belinostat, have been approved by the United States Food and Drug Administration. Principally, these HDAC inhibitors are used for hematologic cancers in clinic with less severe side effects.
What do HDAC enzymes do?
Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl functional groups from the lysine residues of both histone and nonhistone proteins. In humans, there are 18 HDAC enzymes that use either zinc- or NAD+-dependent mechanisms to deacetylate acetyl lysine substrates.
How do HDAC inhibitors work in cancer?
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 [38], is a cause of relative specificity of HDAC inhibitors.
How does HDAC cause cancer?
HDAC repression of epithelial differentiation Loss of expression of proliferation-restraining genes is one common feature of cancer cells. Inhibition of differentiation also causes inappropriate proliferation, which can lead to cancer.
How does HDAC affect transcription?
HATs acetylate lysines of histone proteins, resulting in relaxation of chromatin structure, and they also facilitate gene activation. Conversely, HDACs remove acetyl groups from hyperacetylated histones and suppress general gene transcription.