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论文类型：期刊论文

发表时间：2019-01-01

发表刊物：TURKISH JOURNAL OF HEMATOLOGY

收录刊物：SCIE、PubMed

卷号：36

期号：3

页面范围：162-168

ISSN号：1300-7777

关键字：Ortho-topolin riboside; Differentiation; STAT3 signal; HL-60 cells

摘要：Objective: We previously demonstrated that ortho-topolin riboside (oTR) as a naturally occurring cytokinin secreted from Populus x robusta has great potential anticancer effects via the mitochondrial apoptotic pathway and endoplasmic reticulum stress pathway. In the present study, we reveal that oTR induced the differentiation of acute myeloid leukemia (AML) HL-60 cells, which represent the M2 subtype of AML.
   Materials and Methods: After the incubation of HL-60 cells with oTR, its effect was analyzed with cell viability assay, Wright-Giemsa staining, CD11b protein expression analysis, western blot analysis, and polymerase chain reaction.
   Results: We found that oTR arrested the cell cycle at the S phase, upregulated the expression of myeloid surface marker CD11b, reduced the nuclear cytoplasmic ratio, and altered the horseshoe shape of nuclei, as evidenced by Wright-Giemsa staining. Furthermore, we found that the protein level of phosphorylated STAT3 was decreased when cells were treated with oTR, while phosphorylated STAT1 was activated. Moreover, the protein level of phosphorylated STAT3 and its upstream kinase, Janus kinase 2, were also inhibited when cells were treated with oTR after increased time. Additionally, the levels of phosphorylated SHP-1 were increased while phosphorylated SHP-2 was decreased.
   Conclusion: Collectively, our data indicate a differentiation-induced mechanism underlying the inhibition of STAT3 signaling upon treatment with oTR. Therefore, oTR may constitute a novel differentiation-induced therapeutic for use in clinical treatment of AML.