The clinical significance of histone deacetylase-8 in human breast cancer

Recent studies have shown that the histone deacetylase-8 (HDAC8), as one of the HDACs, regulates the expression and activity of various genes involved in cancer initiation and progression. The HDAC8 plays an epigenetic role to dysregulate expressions or to interact with transcription factors. Most researchers had focused on the HDAC 1-3 and 6, but today the HDAC8 isotype is a promising target in cancer therapy. Different studies, on breast cancer (BC) cells, have recently shown the HDAC8 overexpression and suggested its oncogenic potential. It seems that the HDAC8 could be a novel and promising target in breast cancer treatment. Some studies on BC demonstrated therapeutic properties of the inhibitors of HDAC8 such as suberoylanilide hydroxamic acid (SAHA), Trichostatin A, valproic acid, sodium butyrate, 1,3,4 oxadiazole with alanine hybrid [(R)-2-amino-N-((5-phenyl-1,3,4-oxadiazol-2-yl) methyl) propanamide (10b)], N-(2-Hydroxyphenyl)-2propylpentanamide (compound 2) and PCI-34051. In this review, we highlight the role and existing inhibitors of HDAC8 in BC pathogenesis and therapy.

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S2012 PCI-34051 PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM in a cell-free assay. It has greater than 200-fold selectivity over HDAC1 and 6, more than 1000-fold selectivity over HDAC2, 3, and 10. PCI-34051 induces caspase-dependent apoptosis.

Related Targets

Apoptosis related HDAC