Aim:To study the mechanism by which nanoparticle realgar powders (NRP) in-duce human histocytic lymphoma U937 cell apoptosis.Methods:After the U937 cells were treated with various doses of NRP,the viability of the NRP-induced U937 cells was detected by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay.Granular apoptotic bodies with membrane blebbing and condensed nuclei were observed by fluorescence microscopy.The apoptotic ra-tio induced by NRP was measured by lactate dehydrogenase (LDH) activity-based assay.Caspase-3 and the expressions of Akt,p-Akt,a nicotinamide ad-enine dinucleotide (NAD+)-dependent histone deacetylase (SIRT 1),p53,and p-p53 were detected by Weste blot analysis.Results:The growth-inhibitory activity of NRP for U937 cells was in a time-and dose-dependent manner.After treatment with various concentrations of NRP for 24 h,the majority of U937 cells underwent apoptosis as measured by LDH assay.In the presence of NRP,wortmannin,the inhibitor of phosphoinositide 3-kinase (PI3-K),and Akt inhibitor KP372-1 augmented the NRP-induced cell apoptosis.When the U937 cells were treated with NRP for the indicated time periods,procaspase-3 was gradually de-graded and the activated caspase-3 was significantly increased.The expressions of anti-apoptotic proteins Akt and p-Akt were downregulated.Importantly,the inhibition of SIRT1 contributed to the activation of p53 and the inactivation of the PI3-K/Akt signaling pathway increased the expression of the p53 protein and dowrtregulated the SIRT 1 protein expression.Conclusion:The PI3-K/Akt signal-ing pathway plays an important role in NRP-induced U937 cell apoptosis.The reduced SIRT1 expression and activated p53 might be partially due to the inhibi-tion of the PI3-K/Akt pathway triggered by the NRP-induced initiation of U937 cell apoptosis.