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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
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| Series: | Biochemistry and Biophysics Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825001141 |
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| Summary: | 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. |
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| ISSN: | 2405-5808 |