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Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines Publisher



Abbasi Y1, 2 ; Pooladi M2, 3 ; Nazmabadi R1 ; Amri J4 ; Abbasi H5 ; Karami H1, 6
Authors
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Authors Affiliations
  1. 1. Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
  2. 2. Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
  3. 3. Department of Anatomy, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Biology, Faculty of Sciences, Payame Noor University, Hamedan Branch, Hamedan, Iran
  6. 6. Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

Source: Cell Journal Published:2024


Abstract

Objective: Enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptotic members of the Bcl-2 family proteins, including Bcl-2 and Mcl-1. The aim of this study was to explore the impact of formononetin and dihydroartemisinin combination on the growth and apoptosis of acute myeloid leukemia (AML) cells. Materials and Methods: In this experimental study, the cell survival and cell proliferation were tested by MTT assay and trypan blue staining. The evaluation of cell apoptosis was conducted using Hoechst 33342 staining and a colorimetric assay to measure caspase-3 activity. To determine the mRNA levels of Mcl-1, Bcl-2, Bax, and Cyclin D1, a quantitative real-time polymerase chain reaction (qRT-PCR) was performed. Results: We showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decrease in the cell survival and growth, and triggered apoptosis in U937 and KG-1 AML cell lines. Moreover, treatment with each of the compounds alone significantly decreased the mRNA levels of Mcl-1, Bcl-2 and Cyclin D1 mRNA, while, the expression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect. Conclusion: The anti-leukemic potential of formononetin and dihydroartemisinin is exerted through the effect on cell cycle progression and intrinsic pathway of apoptosis. Therefore, they can be considered as a potential anti-leukemic agent alone or along with existing chemotherapeutic drugs. © 2024 Royan Institute (ACECR). All rights reserved.
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