Sirtinol

Sirtinol is a sirtuin inhibitor, with IC50s of 48 μM, 57.7 μM and 131 μM for ySir2, hSIRT2 and hSIRT2, respectively.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Sirtuin

Signaling Pathways >> Epigenetics >> Sirtuin

Research Areas >> Cancer

ySir2:48 μM (IC50)

hSIRT2:57.7 μM (IC50)

hSIRT1:131 μM (IC50)

Sirtinol reduces the growth of MCF-7 cells in a concentration- and time-dependent manner. The IC50 values of sirtinol are 48.6 μM and 43.5 μM after 24 and 48 h of treatment, respectively. Sirtinol significantly decreases SIRT1 expression and increases the acetylated p53 level[1]. Sirtinol attenuates the proliferation and induces apoptosis of nonsmall cell lung cancer (NSCLC) H1299 cells and causes the significantly increased level of FoxO3a, a proapoptotic transcription factor targeted by Sirt1[2].

Sirtinol has anti-inflammatory effects through direct inhibition of HNE activity and attenuates HNE-induced and LPS-mediated tissue or organ injury[3].

Sirtinol is dissolved in 100% DMSO at concentration of 10 mM and stored at −20°C until use. The cell proliferation of H1299 cells is determined by trypan blue dye exclusion assay. Human nonsmall cell lung cancer (NSCLC) cells are seeded in 12-well plates and treated with indicated concentrations of sirtinol (0, 10, 20, and 50 μM) for 24 h and 48 h, respectively. After incubation, the cells are stained by 0.2% trypan blue and counted by Countess[2].

Mice: 30 male mice (20–25 g, 7–8 weeks old) are used in this model. Briefly, mice are randomly divided into five groups; then mice are intraperitoneally injected with 50 μL DMSO (vehicle group) or sirtinol (2.5 or 5.0 mg/kg body weight). After 1 h, paw inflammation is induced . The thickness of the paw is measured before and after HNE or saline injection[3].

[1]. Wang J, et al. Sirtinol, a class III HDAC inhibitor, induces apoptotic and autophagic cell death in MCF-7 human breast cancer cells. Int J Oncol. 2012 Sep;41(3):1101-1109.

[2]. Fong Y, et al. The antiproliferative and apoptotic effects of sirtinol, a sirtuin inhibitor on human lung cancer cells by modulating Akt/β-catenin-Foxo3a axis. ScientificWorldJournal. 2014;2014:937051.

[3]. Tsai YF, et al. Sirtinol inhibits neutrophil elastase activity and attenuates lipopolysaccharide-mediated acute lung injury in mice. Sci Rep. 2015 Feb 10;5:8347.

[4]. Mai A, et al. Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. J Med Chem. 2005 Dec 1;48(24):7789-95.

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