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The Effects of Abt-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and Kg-1 Cancer Cells Publisher Pubmed



Nazmabadi R1 ; Pooladi M1, 2 ; Amri J3 ; Darvish M1 ; Abbasi Y4 ; Karami H1
Authors
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Authors Affiliations
  1. 1. Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
  2. 2. Department of Anatomy, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

Source: Asian Pacific Journal of Cancer Prevention Published:2024


Abstract

Introduction: Change in the balance of Bcl-2 family proteins is one of the main reasons for resistance of tumor cells to ABT-199. In this study, the effect of dihydroartemisinin on cell growth, apoptosis and sensitivity of the AML cells to ABT-199 was investigated. Methods: Cell proliferation and survival were assessed by trypan blue staining and MTT assay, respectively. Cell apoptosis was measured by Hoechst 33342 staining and caspase-3 activity assay. The expression levels of Bcl-2, Mcl-1 and Bax mRNA were tested by qRT-PCR. Results: Our data showed that combination therapy significantly reduced the IC50 value and synergistically decreased the AML cell survival and growth compared with dihydroartemisinin or ABT-199 alone. Treatment with each of ABT-199 or dihydroartemisinin alone clearly enhanced the Bax mRNA expression and inhibited the expression of Mcl-1 and Bcl-2 mRNA. Inhibition of Mcl-1 mRNA by dihydroartemisinin was associated with enhancement of apoptosis induced by ABT-199 in AML cells. Conclusion: In conclusion, dihydroartemisinin not only triggers the intrinsic pathway of apoptosis, but also can increase the sensitivity of the AML cells to ABT-199 via suppression of Mcl-1 expression. © (2024) This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
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