Induction of TAp63 by histone deacetylase inhibitors

TAp63 belongs to the p53-tumour suppressor family and is capable of transactivating a set of target genesto induce cell cycle arrest and apoptosis. We showed that treatment of cancer cells with chemo-therapeuticdrugs or the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) results in induction of TAp63expression, which is in turn related with chemosensitivity. Indeed, induction of TAp63 by TSA affects sensitivityto chemo-therapeutic drugs via the cleavage of the trans-inhibitory domain of TAp63 by activecaspases, resulting in generation of a transcriptionally hyper-active TAp63 fragment. Therefore therapeuticapproaches that enhance TAp63 expression may offer an improvement in the management of chemoresistanttumours. In this study we tested the abilities of different HDAC inhibitors to induce TAp63expression. We discovered that two HDAC inhibitors belonging to the hydroxamate group, namely TSAand LBH589, are the most efficient inducers of TAp63 expression. Finally, we found that induction ofTAp63 expression in HCT116 cells depends on p53, as p53-negative HCT116 cells failed to induce significantTAp63 expression following treatment with different HDAC inhibitors.