Histone deacetylase inhibition induces apoptosis in neuroblastoma.
Histone deacetylase inhibitors constitute a promising new treatment for cancer due to their novel site of action and low toxicity. Almost all histone deacetylase inhibitors currently in clinical development have anti-proliferate activities against cells in cultures, and specifically cause cell cycle arrest, differentiation and apoptosis. Interestingly, despite their rapid advance into clinical use, the cellular responses leading to these effects remain unclear. We recently reported that histone deacetylase inhibitor treatment induces apoptosis of neuroblastoma cells by increasing the acetylation of Ku70 in the cytoplasm, resulting in the release of Bax from Ku70. Subsequently, Bax releases cytochrome c from mitochondria causing apoptosis. Here we will discuss these findings and the implications of our model for the further clinical development of histone deacetylase inhibitors in the treatment of cancer.
Subramanian
Chitra
C
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Opipari
Anthony W
AW
Castle
Valerie P
VP
Kwok
Roland P S
RP
D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology*
D051033:Apoptosis Inducing Factor; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases