Differential sensitization of hepatocytes by inhibitors of histone deacetylases against death receptor-induced apoptosis

Aims: Preclinical and clinical studies suggest that inhibition of histone/protein deacetylation by targeting histone deacetylases (HDACs) represents a novel approach in cancer therapy [1]. However, only recently it became evident that HDAC inhibitors by themselves do not only induce apoptosis but also render cells sensitive to death receptor agonists, i.e. TNF, TRAIL, and CD95 ligand (CD95L), respectively [2, 3]. For a comprehensive understanding of the pharmacodynamic properties of HDAC inhibitors (HDIs) it is madatory to elucidate and profile these sensitizing effects. Results: HepG2 cells pre-incubated with s…