Sirt6-induced gastric cancer cell death is mediated by Sirt1 suppression. (A) Treatment with 2.5 µM MG-132 (a 26S proteasome inhibitor) for 8 h upregulated Sirt1. (B) Apoptosis, as indicated by the percentage of Sub G1 cells, was significantly decreased via the MG-132 treatment (** p < 0.01). (C) Sirt6 overexpression induced MDM2 and downregulated Sirt1 expression, whereas MDM2 knockdown upregulated Sirt1. (D) Gastric cancer cell death was induced by Sirt6 overexpression and reduced by MDM2 knockdown (*** p < 0.001, ** p < 0.01). (E) Nutlin-3, an MDM2 antagonist, upregulated Sirt1 but did not affect Sirt6 expression levels. (F) Nutlin-3 inhibited gastric cancer cell death (** p < 0.01). (G) Sirt1 was downregulated while Sirt6 was upregulated in the presence of MDM2 in gastric cancer cells.