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

## TL;DR

This study shows that combining telomerase inhibition with natural killer cells increases cancer cell death in Acute Myeloid Leukemia.

## Contribution

The study introduces a novel combination therapy using telomerase inhibition and NK cells to enhance AML treatment.

## Key findings

- Telomerase inhibition with BIBR1532 increases NK cell cytotoxicity against AML cells.
- The combination therapy upregulates pro-apoptotic genes like Bax and downregulates anti-apoptotic genes like Bcl-2.
- Caspase 3/7 activity and Bax/Bcl-2 ratio increase, indicating enhanced apoptosis in AML cells.

## Abstract

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.

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.

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.

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.

Image 1

•Telomerase inhibition sensitizes AML cells in treatment with NK cells.•Inhibition of telomerase increases NK cells cytotoxic activity against AML cells.•Telomerase inhibitor with NK cells boosts apoptosis in AML cells over mono-therapy.

Telomerase inhibition sensitizes AML cells in treatment with NK cells.

Inhibition of telomerase increases NK cells cytotoxic activity against AML cells.

Telomerase inhibitor with NK cells boosts apoptosis in AML cells over mono-therapy.