Abstract
The epigenetic regulation of gene expression is controlled by various processes, of which one is histone acetylation. Many proteins control gene expression via histone acetylation. Those proteins include sirtuins (SIRTs) and bromodomain and extraterminal proteins (BETs), which are known to regulate same cellular processes and pathways. The aim of this study was to explore BET inhibitors' effects on SIRT1. Previously we showed that BET inhibitor (+)-JQ1 increases SIRT1 levels, but in the current study we used also other, structurally diverse BET inhibitors, I-BET151 and Pfi-1, and examined their effects on SIRT1 levels in two breast cancer cell lines. The results differed between the inhibitors and also between the cell lines. (+)-JQ1 had opposite effects on SIRT1 levels in the two cell lines, I-BET151 increased the levels in both cell lines, and Pfi-1 had no effect. In conclusion, the effect of structurally diverse BET inhibitors on SIRT1 levels is divergent, and the responses might also be cell type-dependent. These findings are important for all SIRT1 and BET inhibitor-related research, and they show that different BET inhibitors might have important individual effects.