Indexed by:Journal Papers
Date of Publication:2019-05-23
Journal:Turkish journal of haematology : official journal of Turkish Society of Haematology
Included Journals:PubMed
ISSN No.:1308-5263
Key Words:Ortho-topolin riboside,differentiation,STAT3 signal,HL-60 cells
Abstract:We previously demonstrated that ortho-topolin riboside (oTR), a naturally occurring cytokinin, exhibits potential anticancer effects via the mitochondrial apoptotic pathway and endoplasmic reticulum stress pathway. In the present study, we revealed that oTR induced the differentiation of acute myeloid leukemia (AML) HL-60 cells, which represent the M2 sub-type of AML. We found that oTR arrested the cell cycle at 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. Further, we found that oTR reduced the protein level of phosphorylated STAT3 and activated the protein level of phosphorylated STAT1, but not total STAT1 and STAT3. Moreover, we found time-dependent inhibition of the expression of both phosphorylated STAT3 and its upstream kinase, Janus kinase 2, when cells were treated with oTR. Additionally, the levels of phosphorylated SHP-1 were increased while phosphorylated SHP-2 was decreased. 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.