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

• Published in: Cell journal (Yakhteh) Vol. 26; no. 2; pp. 121 - 129
• Main Authors: Abbasi, Yusef, Pooladi, Marziyeh, Nazmabadi, Roya, Amri, Jamal, Abbasi, Helia, Karami, Hadi
• Format: Journal Article
• Language: English
• Published: Iran Royan Institute of Iran 01.02.2024; Royan Institute; Royan Institute (ACECR), Tehran
• Subjects: Acute myeloid leukemia; Anticancer properties; Antineoplastic drugs; Apoptosis; BAX protein; bcl-2; Bcl-2 protein; Caspase-3; Cell cycle; Cell proliferation; Cell survival; Chemotherapy; Colorimetry; Cyclin D1; Dihydroartemisinin; Drug resistance; formononetin; Gene expression; Leukemia; mcl-1; Mcl-1 protein; mRNA; Original; Polymerase chain reaction; Staining; Survival; Tumor cell lines; Tumor cells; Bcl-2; Dihydroartemisinin; Mcl-1; Acute Myeloid Leukemia; Formononetin; Apoptosis
• ISSN: 2228-5806; 2228-5814
• DOI: 10.22074/CELLJ.2024.2016937.1459

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. 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 , a quantitative real-time polymerase chain reaction (qRT-PCR) was performed. 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 and mRNA, while, the expression level of Bax mRNA was enhanced. Combination of two compounds showed a synergistic anti-cancer effect. 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.