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

Document Type : Original Article


1 Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

2 Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

3 Department of Anatomy, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Biology, Faculty of Sciences, Payame Noor University, Hamedan Branch, Hamedan, Iran

6 Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran


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.


Main Subjects

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