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

Background: 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.

Objective: 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.

Material and methods: 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.

Results: 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).

Conclusions: 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.