The synergistic effect of 2-deoxy-D-glucose and Cytarabine on mitochondria of Stem-like cells derived from KG1-a

Abstract

Background: Acute myeloid leukemia (AML) has a high probability of recurrence 5 years after treatment with traditional chemotherapy. One of the factors that play a role in AML relapses is the presence of leukemia stem cells (LSCs). Many vital roles of mitochondria such as energy production, oxidation-reduction status, Reactive oxygen species (ROS) production, control of cytosolic calcium levels, and initiation of apoptosis, these organelles carry out an important role in developing LSCs. Metabolic flexibility and mitochondrial dependence are two important requirements of LSCs resistance to chemotherapy. Therefore, it would be reasonable to target mitochondria in cancer treatment. Method and result: In this study, an acute myeloid leukemia-derived cell line i.e., KG1-a was treated with different concentrations of Cytarabine (Ara-c), 2-Deoxy-D-Glucose (2-DG), and their combination. The effects of different treatments were assessed by MTT assay and calculated synergistic index. Then, The Magnetic Antibody Cell Sorting (MACS) was used to isolate cancer CD34+ and CD34- cells as representatives of leukemia stem-like cells and other leukemia cells, respectively. Flow cytometric dyes DCFH-da and Rhodamine 123 were used to evaluate the production of ROS and mitochondrial membrane potential (MMP) in the cells, respectively. Conclusion: We found that 2-DG and Ara-c have synergistic effects on KG1-a, as well as their combination increases ROS production and reduces MMP, significantly. It seems that combination treatment is the best choice to target more resistant stem-like cells.