Abstract

This study aims to enhance efficacy and reduce toxicity of the combination treatment of a drug and curcumin (Cur) on leukemic stem cell and leukemic cell lines, including KG-1a and KG-1 (FLT3+ LSCs), EoL-1 (FLT3+ LCs), and U937 (FLT3− LCs). The cytotoxicity of co-treatments of doxorubicin (Dox) or idarubicin (Ida) at concentrations of the IC10–IC80 values and each concentration of Cur at the IC20, IC30, IC40, and IC50 values (conditions 1, 2, 3, and 4) was determined by MTT assays. Dox–Cur increased cytotoxicity in leukemic cells. Dox–Cur co-treatment showed additive and synergistic effects in several conditions. The effect of this co-treatment on FLT3 expression in KG-1a, KG-1, and EoL-1 cells was examined by Western blotting. Dox–Cur decreased FLT3 protein levels and total cell numbers in all the cell lines in a dose-dependent manner. In summary, this study exhibits a novel report of Dox–Cur co-treatment in both enhancing cytotoxicity of Dox and inhibiting cell proliferation via FLT3 protein expression in leukemia stem cells and leukemic cells. This is the option of leukemia treatment with reducing side effects of chemotherapeutic drugs to leukemia patients.

Highlights

  • Introduction published maps and institutional affilLeukemia is among the top 10 cancers diagnosed globally

  • Leukemia can be divided into four major types according to the stage and cell of origin: acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL)

  • The aims of this study were determined the cytotoxicity of co-treatment with anthracycline drugs and curcumin for FLT3-overexpressing leukemic stem cells

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Summary

Introduction

Leukemia is among the top 10 cancers diagnosed globally It is a group of cancers of early blood-forming cells, which are characterized by the uncontrolled production and accumulation of blast or immature abnormal blood cells in the peripheral blood and bone marrow. AML is the most common type of acute leukemia in adults, with the highest incidence and death rate in both sexes. It can be distinguished by clonal expansion of abnormal myeloid blasts in bone marrow, peripheral blood, or other tissues. 15–25% of AML patients fail to achieve complete remission (CR) due to chemotherapy resistance and may show relapse, with the overall 5-year survival rate of approximately 40% [1,2]. Between 10 and 40% of newly diagnosed AML patients do not achieve CR with intensive iations

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