formononetin and dihydroartemisinin act synergistically to induce apoptosis in human acute myeloid leukemia cell lines

Objective: enhanced cell survival and drug resistance in tumor cells have been linked to the overexpression of antiapoptoticmembers of the bcl-2 family proteins, including bcl-2 and mcl-1. the aim of this study was to explore theimpact 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 andtrypan blue staining. the evaluation of cell apoptosis was conducted using hoechst 33342 staining and a colorimetricassay to measure caspase-3 activity. to determine the mrna levels of mcl-1, bcl-2, bax, and cyclin d1, a quantitativereal-time polymerase chain reaction (qrt-pcr) was performed.results: we showed that treatment with either formononetin or dihydroartemisinin alone, led to significant decreasein the cell survival and growth, and triggered apoptosis in u937 and kg-1 aml cell lines. moreover, treatment witheach of the compounds alone significantly decreased the mrna levels of mcl-1, bcl-2 and cyclin d1 mrna, while, theexpression 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 cellcycle progression and intrinsic pathway of apoptosis. therefore, they can be considered as a potential anti-leukemicagent alone or along with existing chemotherapeutic drugs.