Ortho-topolin riboside induced cell apoptosis through ERS pathway and inhibited DNMT1 activity in acute myeloid leukemia cells

Abstract

We previously demonstrated that ortho-topolin riboside (oTR), a naturally occurring phytohormone, has potential anticancer effects via the mitochondrial apoptotic pathway in acute promyelocytic leukemia HL-60 cells and hepatocellular carcinoma SMMC-7721 cells. In the present study, we showed that oTR inhibited the of acute myeloid leukemia (AML) U937 cells. Cellular adenosine transporte uptake of oTR but not adenosine receptors was involved in the growth inhibition. We also found oTR induced cell apoptosis through the Endoplasmic Reticulum Stress (ERS) pathway, as evidenced by the upregulation of the ERS regulator glucose regulated protein 78. Exposure of U937 cells to oTR upregulated the surface marker CD11b, reduced the nuclear cytoplasmic ratio, and altered the horseshoe shape of nuclei, as determined by Wright-Giemsa staining. Further we found that oTR as an effective inhibitor decrease the DNA methyltransferase 1 (DNMT1) activity in a dose-dependent manner. Dock study showed that oTR can dock to the putative pocket of the DNMT1. We concluded that oTR induced apoptosis, promoted the cell differentiation and inhibited DNMT1 activity of U937 cells, suggesting its potential as a therapeutic agent for the treatment of AML.