Comparative transcriptional study after treatment with the HDAC inhibitor Trichostatin A

Based on the hypothesis that a universal mechanism of cell death induction by HDAC inhibitors exists, a comparative study of differential gene expression after treatment with TSA has been conducted in both hematopoietic and solid tumor cell lines sensitive to TSA-induced cell death, in certain resistant cell lines, and in a sensitive cell line in the presence of the serine protease inhibitor AEBSF, which blocks TSA-induced cell death in all tested human and mouse models sensitive to the drug.

The aim was to identify deregulated genes common to all TSA-sensitive models but not present in resistant lines, and whose deregulation is also prevented in the presence of AEBSF. We used Affymetrix arrays to analyze samples from cell lines derived from hematopoietic neoplasms and solid tumors, both murine and human, which were either sensitive or resistant to Trichostatin A-induced cell death, as well as some sensitive cell lines treated with the serine protease inhibitor AEBSF, which is capable of blocking this cell death in all tested systems.