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...
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| Language: | English |
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Royan Institute (ACECR), Tehran
2024-02-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_710541_0553177dfa869a03170b0acd034b3444.pdf |
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| author | Yusef Abbasi Marziyeh Pooladi Roya Nazmabadi Jamal Amri Helia Abbasi Hadi Karami |
| author_facet | Yusef Abbasi Marziyeh Pooladi Roya Nazmabadi Jamal Amri Helia Abbasi Hadi Karami |
| author_sort | Yusef Abbasi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T01:24:46Z |
| format | Article |
| id | doaj.art-7b41c65b58e64be8b2a0ba6db161b067 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-04-25T01:24:46Z |
| publishDate | 2024-02-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-7b41c65b58e64be8b2a0ba6db161b0672024-03-09T07:20:35ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142024-02-0126212112910.22074/cellj.2024.2016937.1459710541Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell LinesYusef Abbasi0Marziyeh Pooladi1Roya Nazmabadi2Jamal Amri3Helia Abbasi4Hadi Karami5Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, IranDepartment of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, IranTraditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Biology, Faculty of Sciences, Payame Noor University, Hamedan Branch, Hamedan, IranTraditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, IranObjective: 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.https://www.celljournal.org/article_710541_0553177dfa869a03170b0acd034b3444.pdfacute myeloid leukemiaapoptosisbcl-2dihydroartemisininformononetinmcl-1 |
| spellingShingle | Yusef Abbasi Marziyeh Pooladi Roya Nazmabadi Jamal Amri Helia Abbasi Hadi Karami Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines Cell Journal acute myeloid leukemia apoptosis bcl-2 dihydroartemisinin formononetin mcl-1 |
| title | Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines |
| title_full | Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines |
| title_fullStr | Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines |
| title_full_unstemmed | Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines |
| title_short | Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines |
| title_sort | formononetin and dihydroartemisinin act synergistically to induce apoptosis in human acute myeloid leukemia cell lines |
| topic | acute myeloid leukemia apoptosis bcl-2 dihydroartemisinin formononetin mcl-1 |
| url | https://www.celljournal.org/article_710541_0553177dfa869a03170b0acd034b3444.pdf |
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