Induction of TAp63 by histone deacetylase inhibitors

Area of Science:

• Molecular Biology
• Cancer Research
• Pharmacology

Background:

• TAp63, a member of the p53 tumor suppressor family, regulates genes involved in cell cycle arrest and apoptosis.
• Chemotherapeutic drugs and HDAC inhibitors like Trichostatin A (TSA) can induce TAp63 expression, correlating with chemosensitivity.
• TAp63's sensitivity to chemotherapy is modulated by caspase-mediated cleavage, generating a more active fragment.

Purpose of the Study:

• To investigate the efficacy of various HDAC inhibitors in inducing TAp63 expression.
• To explore therapeutic strategies for enhancing TAp63 expression in chemoresistant tumors.

Main Methods:

• Treatment of cancer cells with different HDAC inhibitors.
• Assessment of TAp63 expression levels.
• Analysis of p53 dependency for TAp63 induction.

Main Results:

• The hydroxamate HDAC inhibitors TSA and LBH589 were identified as potent inducers of TAp63 expression.
• TAp63 induction by HDAC inhibitors was found to be dependent on the presence of p53.
• p53-negative HCT116 cells showed significantly less TAp63 induction upon HDAC inhibitor treatment.

Conclusions:

• HDAC inhibitors, particularly TSA and LBH589, effectively induce TAp63 expression.
• p53 is essential for the induction of TAp63 by HDAC inhibitors in HCT116 cells.
• Targeting TAp63 induction via HDAC inhibitors presents a promising therapeutic avenue for overcoming chemoresistance in tumors.