The Mechanisms of Piceatannol in Inhibiting the Malignant Biological Characteristics of Acute Myeloid Leukemia Cells

Abstract

To explore the effect and molecular mechanism of Piceatannol on malignant biological characteristics of acute myeloid leukemia (AML) cells. HL60, U937, HL60/ADR and U937/ADR cells were treated with different concentrations of Piceatannol. CCK-8 assay was used to detect cell proliferation. Cell apoptosis was detected by flow cytometry with Annexin V/PI double staining. The protein expressions of apoptosis, autophagy and related signaling pathways were detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression changes of drug resistance genes in drug-resistant AML cell lines. The activity of HL60 and U937 cells could be inhibited by Piceatannol and induced apoptosis. When Piceatannol interfered with AML cells for 24 h, the ratio of autophagy marker LC3-II/LC3-I increased with the increase of concentration (r=0.672， r=0.549). When Piceatannol interfered with AML cells for 48 h, the expression of Bcl-2 protein was down-regulated and caspase-3 was hydrolyzed and activated. At the same time, the activation level of Akt/NF-κB signaling pathway was inhibited to induce programmed death of AML cells. Piceatannol can also down-regulate the expression of MRP1 and gradually weaken the chemotherapy resistance of AML drug-resistant cell lines, but it has a weak effect on the expression of BCRP and almost no effect on MDR1. Piceatannol can inhibit the proliferation of AML cells and induce programmed death, which may be related to the inhibition of Akt/NF-κB signaling pathway, the hydrolysis of caspase-3 and the down-regulation of Bcl-2 protein expression, and the suppression of the expression of some drug resistance genes.