Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells
Background: Recent trends in developing new treatments for cancers, highlight the use of immune cells particularly Natural Killer (NK) cells, as promising therapeutic strategies. While NK cells exhibit significant anti-tumor effects, their effectiveness is often limited. This study investigated the...
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Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825001141 |
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| author | Ali Rafat Khadijeh Dizaji Asl Zeinab Mazloumi Mehdi Talebi Hojjatollah Nozad Charoudeh |
| author_facet | Ali Rafat Khadijeh Dizaji Asl Zeinab Mazloumi Mehdi Talebi Hojjatollah Nozad Charoudeh |
| author_sort | Ali Rafat |
| collection | DOAJ |
| description | Background: Recent trends in developing new treatments for cancers, highlight the use of immune cells particularly Natural Killer (NK) cells, as promising therapeutic strategies. While NK cells exhibit significant anti-tumor effects, their effectiveness is often limited. This study investigated the impact of BIBR1532, a human telomerase reverse transcriptase (hTERT) inhibitor, on improving the cytotoxicity of NK cells against Acute Myeloid Leukemia (AML) cells. Methods: Primary AML cells and Kg-1a cell lines were cultured and treated with the half-maximal inhibitory concentration (IC50) of BIBR1532 for 48 h. The treated cells were then co-cultured with NK cells, after which cytotoxicity, cell proliferation, and apoptosis were assessed using Annexin V/7-AAD and Ki-67 expression analysis. Finally, apoptosis-related genes and proteins, hTERT gene and caspase 3/7 activity were studied. Results: The Telomerase Inhibition (TI) in primary AML and Kg-1a cells with IC50 values of 38.75 μM and 57.64 μM, respectively, sensitized the AML cells and enhanced the anti-proliferative effects of NK cells. The combination of BIBR1532 and NK cells led to increased apoptosis, as indicated by the upregulation of the Bax and Bad genes, an increased Bax/Bcl-2 ratio, caspase 3/7 activity, Bax protein and a downregulation of mRNA expression levels of Bcl-2, Bcl-xl and decreased Bcl-2 protein. Conclusion: The findings of this study demonstrate that the concurrent application of BIBR1532 and NK cells promotes apoptosis and reduces proliferation by targeting apoptosis-related genes and proteins such as Bax and Bcl-2. |
| format | Article |
| id | doaj-art-a9d0aed629e74843b76fec33c43f34ac |
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| issn | 2405-5808 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-a9d0aed629e74843b76fec33c43f34ac2025-08-20T02:17:09ZengElsevierBiochemistry and Biophysics Reports2405-58082025-06-014210202710.1016/j.bbrep.2025.102027Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cellsAli Rafat0Khadijeh Dizaji Asl1Zeinab Mazloumi2Mehdi Talebi3Hojjatollah Nozad Charoudeh4Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, IranDepartment of Histopathology and Anatomy, Faculty of Medical Sciences, Tabriz Medical Sciences, Islamic Azad University, Tabriz, IranDepartment of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Scientific Center of Zoology and Hydroecology, NAS RA, Yerevan, Armenia; Corresponding author. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Scientific Center of Zoology and Hydroecology, NAS RA, Paruyr Sevak St. 7, Yerevan, 0014, Armenia.Background: Recent trends in developing new treatments for cancers, highlight the use of immune cells particularly Natural Killer (NK) cells, as promising therapeutic strategies. While NK cells exhibit significant anti-tumor effects, their effectiveness is often limited. This study investigated the impact of BIBR1532, a human telomerase reverse transcriptase (hTERT) inhibitor, on improving the cytotoxicity of NK cells against Acute Myeloid Leukemia (AML) cells. Methods: Primary AML cells and Kg-1a cell lines were cultured and treated with the half-maximal inhibitory concentration (IC50) of BIBR1532 for 48 h. The treated cells were then co-cultured with NK cells, after which cytotoxicity, cell proliferation, and apoptosis were assessed using Annexin V/7-AAD and Ki-67 expression analysis. Finally, apoptosis-related genes and proteins, hTERT gene and caspase 3/7 activity were studied. Results: The Telomerase Inhibition (TI) in primary AML and Kg-1a cells with IC50 values of 38.75 μM and 57.64 μM, respectively, sensitized the AML cells and enhanced the anti-proliferative effects of NK cells. The combination of BIBR1532 and NK cells led to increased apoptosis, as indicated by the upregulation of the Bax and Bad genes, an increased Bax/Bcl-2 ratio, caspase 3/7 activity, Bax protein and a downregulation of mRNA expression levels of Bcl-2, Bcl-xl and decreased Bcl-2 protein. Conclusion: The findings of this study demonstrate that the concurrent application of BIBR1532 and NK cells promotes apoptosis and reduces proliferation by targeting apoptosis-related genes and proteins such as Bax and Bcl-2.http://www.sciencedirect.com/science/article/pii/S2405580825001141Acute myeloid leukemiaApoptosisNatural killer cellTelomerase |
| spellingShingle | Ali Rafat Khadijeh Dizaji Asl Zeinab Mazloumi Mehdi Talebi Hojjatollah Nozad Charoudeh Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells Biochemistry and Biophysics Reports Acute myeloid leukemia Apoptosis Natural killer cell Telomerase |
| title | Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells |
| title_full | Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells |
| title_fullStr | Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells |
| title_full_unstemmed | Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells |
| title_short | Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells |
| title_sort | natural killer cells in combination with the inhibition of telomerase induced apoptosis in acute myeloid leukemia cells |
| topic | Acute myeloid leukemia Apoptosis Natural killer cell Telomerase |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825001141 |
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