Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7.

Abstract

To date, the main clinical interest in DPP4 is focused on its inhibition in diabetic patients to prolong the half-life of incretins. Epigenetic alterations resulting from DPP4 inhibition have been poorly explored. The objective of this study was to determine, whether sitagliptin, a DPP4 inhibitor, has effects on the expression of KAT7 and SIRT1 (genes encoding a histone acetyltransferase and a histone deacetylase, respectively) in MCF7 breast cancer cells, which play an essential role in modulating the epigenetic landscape of chromatin. MCF7 cells were incubated for 20 h with sitagliptin at concentrations of 0.5, 1.0 and 2.0 μM. Total RNA was isolated and the relative mRNA expression of KAT7 and SIRT1 was determined by RT-qPCR. There was downregulation in the relative expression of both genes; for KAT7, downregulation reached up to 0.49 (p = 0.027) and for SIRT1, it reached up to 0.55 (p = 0.037). These results suggest that sitagliptin has effects on the histone epigenetic landscape. This topic deserves further study due to the current sample use of DPP4 inhibitors in diabetic patients.