Background:

SRT1720 is a small-molecule compound which has the ability of activating the sirtuin subtype SIRT1 in vitro. The activity of SRT1720 as a SIRT1 activator is stronger than that of resveratrol. It affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. SRT1720 has been demonstrated to enhance insulin sensitivity and improve measures of mitochondrial capacity and oxidative metabolism. Treatment of multiple myeloma (MM) cells with SRT1720 inhibits growth and induced apoptosis in MM cells resistant to conventional and bortezomib therapies without significantly affecting the viability of normal cells. SRT1720 is able to enhance the cytotoxic activity of bortezomib or dexamethasone. Anti-MM activity of SRT1720 is related to: 1) activation of caspase-8, caspase-9, caspase-3, poly(ADP) ribose polymerase; 2) increase in reactive oxygen species; 3) induction of phosphorylated ataxia telangiectasia mutated/checkpoint kinase 2 signaling; 4) decrease in vascular endothelial growth factor-induced migration of MM cells and associated angiogenesis; and 5) inhibition of nuclear factor-κB.

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