HDAC inhibitors: roles of DNA damage and repair.

摘要: Histone deacetylase inhibitors (HDACis) increase gene expression through induction of histone acetylation. However, it remains unclear whether specific changes determine the apoptotic response following HDACis administration. Herein, we discuss evidence that trigger in cancer and leukemia cells not only widespread acetylation but also actual increases reactive oxygen species (ROS) DNA damage are further increased treatment with DNA-damaging chemotherapies. While origins ROS production completely understood, mechanisms, including inflammation altered antioxidant signaling, have been reported. generation is an explanation, at least part, for source observed HDACi treatment, can be independently induced by repair activity chromatin remodeling factors. Recent development sirtuin (SIRTis) has shown that, similar to HDACis, these drugs induce used singly, or combination other drugs. Thus, apoptosis HDACis/SIRTis may result oxidative stress mechanisms addition direct activation apoptosis-inducing genes. Nevertheless, while responses could interest as markers clinical responses, they yet validated trials, alone, combination.