Work

Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells

Year: 2025

Type: article

Abstract: 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.

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2025.102027

Authors: Ali Rafat, Khadijeh Dizaji Asl, Zeinab Mazloumi, Mehdi Talebi, Hojjatollah Nozad Charoudeh

Institutions: Tabriz University of Medical Sciences, Kashan University of Medical Sciences, Islamic Azad University of Tabriz, Scientific Center of Zoology and Hydroecology, National Academy of Sciences of Armenia

Language: English

Topic: Immune Cell Function and Interaction

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700